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Di Tommaso, Luca,Destro, Annarita,Seok, Jae Yeon,Balladore, Emanuela,Terracciano, Luigi,Sangiovanni, Angelo,Iavarone, Massimo,Colombo, Massimo,Jang, Ja June,Yu, Eunsil,Jin, So Young,Morenghi, Emanuela Elsevier 2009 Journal of hepatology Vol.50 No.4
<P><B>Background/Aims</B></P><P>Liver biopsy for hepatocellular carcinoma (HCC) detection is largely restricted to small hepatocellular lesions, which are often morphologically challenging, requiring careful distinction between dysplastic nodules (high-grade) and well-differentiated HCC.</P><P><B>Methods</B></P><P>We investigated the diagnostic accuracy of a panel of markers (HSP70 GPC3 and GS), previously tested in resection specimens, in a series of liver biopsies of large regenerative nodules (<I>n</I>=13), low-grade dysplastic nodules (<I>n</I>=21), high-grade dysplastic nodules (<I>n</I>=50), very well-differentiated (VWD) (<I>n</I>=17), well-differentiated (WD-G1) (<I>n</I>=40) and G2-3 (<I>n</I>=35) HCC.</P><P><B>Results</B></P><P>Almost all cases of large regenerative and low-grade dysplastic nodules did not stain while high-grade dysplastic nodules showed 1 marker (22%) but never 2 or 3. For HCC detection the overall accuracy of marker combination was 60.8% (3 markers) and 78.4% (2 markers) with 100% specificity. When restricted to VWD+WD-G1 HCC the accuracy was 57% (3 markers) and 72.9% (2 markers) with 100% specificity.</P><P><B>Conclusions</B></P><P>This panel proved useful to detect well-differentiated HCC in biopsy. Two immunoreactive markers (out of 3) are recommended as the most valuable diagnostic combination for HCC detection. The diagnostic accuracy of the panel could be improved using additional markers, as suggested by studies of expression profiling in other human models.</P>
Di Tommaso, Luca,Franchi, Giada,Park, Young Nyun,Fiamengo, Barbara,Destro, Annarita,Morenghi, Emanuela,Montorsi, Marco,Torzilli, Guido,Tommasini, Maurizio,Terracciano, Luigi,Tornillo, Luigi,Vecchione, Wiley Subscription Services, Inc., A Wiley Company 2007 Hepatology Vol.45 No.3
<P>Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC-G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC-G1 are involved. We investigated the diagnostic yield of a panel of 3 putative markers of hepatocellular malignancy such as HSP70, glypican 3 (GPC3), and glutamine synthetase (GS). We selected 52 surgically removed nonmalignant nodules (15 LRNs, 15 LGDNs, 22 HGDNs) and 53 HCCs (10 early, 22 grade 1, and 21 grade 2-3) and immunostained them for HSP70, GPC3, and GS. The sensitivity and specificity of the individual markers for the detection of eHCC-G1 were 59% and 86% for GS, 69% and 91% for GPC3, and 78% and 95% for HSP70. We identified 2 main phenotypes: (1) all negative, seen in 100% LRN and LGDN, 73% HGDN and 3% eHCC-G1; (2) all positive, a feature detected in less than half the eHCC-G1. Using a 3-marker panel, when at least 2 of them, regardless which, were positive, the sensitivity and specificity for the detection of eHCC-G1 were respectively 72% and 100%; the most sensitive combination was HSP70+/GPC3+ (59%) when a 2-marker panel was used. Conclusion: The adopted panel of 3 markers is very helpful in distinguishing eHCC-G1 from dysplastic nodules arising in cirrhosis. (HEPATOLOGY 2007;45:725–734.)</P>
Changes in Speech Range Profile Are Associated with Cognitive Impairment
De Stefano Alessandro,Di Giovanni Pamela,Kulamarva Gautham,Di Fonzo Francesca,Massaro Tommaso,Contini Agnese,Dispenza Francesco,Cazzato Claudio 대한치매학회 2021 Dementia and Neurocognitive Disorders Vol.20 No.4
Background and Purpose: The aim of this study was to describe the variations in the speech range profile (SRP) of patients affected by cognitive decline. Methods: We collected the data of patients managed for suspected voice and speech disorders, and suspected cognitive impairment. Patients underwent an Ear Nose and Throat evaluation and Mini-Mental State Examination (MMSE). To obtain SRP, we asked the patients to read 18 sentences twice, at their most comfortable pitch and loudness as they would do in daily conversation, and recorded their voice on to computer software. Results: The study included 61 patients. The relationship between the MMSE score and SRP parameters was established. Increased severity of the MMSE score resulted in a statistically significant reduction in the average values of the semitones to the phonetogram, and the medium and maximum sound pressure levels (p<0.001). The maximum predictivity of MMSE was based on the highly significant values of semitones (p<0.001) and the maximum sound pressure levels (p=0.010). Conclusions: The differences in SRP between the various groups were analyzed. Specifically, the SRP value decreased with increasing severity of cognitive decline. SRP was useful in highlighting the relationship between all cognitive declines tested and speech.
A clinical and pathological update on hepatocellular carcinoma
( Salvatore Lorenzo Renne ),( Luca Di Tommaso ) 대한간암학회 2022 대한간암학회지 Vol.22 No.1
It is estimated that more than 1 million individuals will be affected annually by hepatocellular carcinoma (HCC) by 2025. HCC can be broadly grouped into two major molecular subgroups, each of which is characterized by specific morphological and phenotypic features that mirror the genetic background. The use of these tissue biomarkers in the daily practice of pathologists promises to better allocate patients with HCC with adequate treatments. In turn, this will likely boost the attitude of clinicians toward obtaining a pre-treatment biopsy. (J Liver Cancer 2022;22:14-22)
Eugenia Fragalà,Giorgio Ivan Russo,Alessandro Di Rosa,Raimondo Giardina,Salvatore Privitera,Vincenzo Favilla,Francesco Patti,Blayne Welk,Sebastiano Cimino,Tommaso Castelli,Giuseppe Morgia 대한배뇨장애요실금학회 2015 International Neurourology Journal Vol.19 No.4
Purpose: To determine the relationship between the neurogenic bladder symptoms score (NBSS) and urodynamic examination in patients affected by multiple sclerosis (MS) and related lower urinary tract dysfunction (LUTD). Methods: We recruited 122 consecutive patients with MS in remission and LUTD from January 2011 to September 2013 who underwent their first urodynamic examination. Neurological impairment was assessed using the Expanded Disability Status Scale (EDSS) and bladder symptoms were studied with the NBSS. Results: Median NBSS was 20.0 (interquartile range, 12.75–31.0). Neurogenic detrusor overactivity (NDO) was discovered in 69 patients (56.6%). The concordance between patients with NDO and maximum detrusor pressure during involuntary detrusor contraction (PdetmaxIDC)≥20.0 cm H2O was 0.89 (κ-Cohen; P<0.05). Patients with EDSS scores of ≥4.5 had a greater NBSS (25.41 vs. 20.19, P<0.05), NBSS-incontinence (8.73 vs. 4.71, P<0.05), NBSS-consequence (4.51 vs. 3.13, P<0.05) and NBSS-quality of life (2.14 vs. 1.65, P<0.05). The NBSS was not associated with PdetmaxIDC≥20 cm H2O (P=0.77) but with maximum cystometric capacity<212 mL (odds ratio, 0.95; P<0.05). Conclusions: The NBSS cannot give adequate information the way urodynamic studies can, in patients with MS and LUTD.
Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma
( Massimo Roncalli ),( Amedeo Sciarra ),( Luca Di Tommaso ) 대한간학회 2016 Clinical and Molecular Hepatology(대한간학회지) Vol.22 No.2
Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed. (Clin Mol Hepatol 2016;22:199-211)
Park, Young Nyun,Kojiro, Masamichi,Di Tommaso, Luca,Dhillon, Amar P.,Kondo, Fukuo,Nakano, Masayuki,Sakamoto, Michiie,Theise, Neil D.,Roncalli, Massimo John Wiley & Sons 2007 Cancer Vol.109 No.5
<B>BACKGROUND.</B><P>Stromal invasion is 1 of the main features used to distinguish high-grade dysplastic nodules (DNs) from well-differentiated hepatocellular carcinomas (HCCs). The authors hypothesized that ductular reaction (DR) takes place around noninvasive hepatocellular nodules but not within the stroma contiguous to invasive HCC.</P><B>METHODS.</B><P>DR/cytokeratin 7 (CK7)-positive patterns were evaluated in 105 resected small hepatic nodules according to the level of invasion. The nodules were classified histologically prior to immunostaining as noninvasive (large regenerative nodules, low-grade DNs, and high-grade DNs), minimally invasive (early HCCs with a vaguely nodular type), and overtly invasive (typical HCCs with a distinctly nodular type) in a review by expert pathologists, the current gold standard. Intranodular DR (inner DR) and DR around the nodule periphery (outer DR) were assessed separately on a semiquantitative scale from 0 to 4+.</P><B>RESULTS.</B><P>DR was 3 or 4+ in the majority of noninvasive nodules (inner DR, 81%; outer DR, 91%), whereas DR was 0 or 1+ in overtly invasive HCCs (inner DR, 96%; outer DR, 81%). Minimally invasive HCCs showed an intermediate DR pattern (2 or 3+ inner DR, 75%; 2+ outer DR, 67%). DR characteristically was absent at the stromal-invasive, leading edge of tumor cells in both minimally invasive HCCs (focal loss of DR/CK7) and overtly invasive HCCs (diffuse loss of DR/CK7). The DR patterns in 41 needle-biopsy samples were similar to the patterns observed in resected nodules.</P><B>CONCLUSIONS.</B><P>DR/CK7 immunostaining may help to identify small foci of invasion and to distinguish noninvasive, high-grade DNs from both minimally invasive and overtly invasive HCCs. Cancer 2007 © 2007 American Cancer Society.</P>
Elena Formisano,Andrea Pasta,Anna L. Cremonini,Elda Favari,Annalisa Ronca,Federico Carbone,Tommaso Semino,Francesco Di Pierro,Samir G. Sukkar,Livia Pisciotta 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.6
The guidelines for the treatment of dyslipidemias include the use of nutraceuticals (NUTs) in association with lifestyle modifications to achieve therapeutic goals. In NUT pill, different substances may be associated; in this study we investigated a combined NUT containing monacolin K (MonK)+KA (1:1), berberine (BBR), and silymarin. The aim of the study was to evaluate low-density lipoprotein cholesterol (LDL-C) reduction in 53 patients suffering from polygenic hypercholesterolemia, characterized by a low/intermediate cardiovascular risk calculated with SCORE algorithm. The effects on lipid profile of 2-month treatment with NUT containing MonK+KA (1:1), BBR, and sylimarin, were compared with Atorvastatin (ATO) 10 mg administrated in a matched control group. Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the cholesterol loading capacity (CLC) were determined at baseline and at the end of the study in NUT-treated group; variations were assessed. NUT was effective as lipid-lowering agent with a wide interindividual response variability (mean LDL-C from 170.8 ± 19.9 to 123.8 ± 20.0 with a change of −47.0 ± 21.5 mg/dL; P < .001) and the effect was similar to that induced by ATO. The use of NUT significantly modified PCSK9 levels (P < .01) and CLC (P < .001), ultimately suppressing the serum-mediated foam cell generation directly measured on human macrophages. NUT reduces LDL-C levels with an effect similar to what is induced by 10 mg of ATO and ex vivo improves the functional profile of lipoproteins with antiatherogenic action.