Decreasing Albumin mRNA Expression in Cholangiocarcinomas along the Bile Duct Tree.

INTRODUCTION: The progressive technologies in albumin in situ hybridization (ISH) changed the routine application and the differential diagnosis of hepatic malignancies in the last years. The aim of the present work was to assess the diagnostic utility of albumin ISH on different cholangiocarcinoma (CCA) subtypes, as well as to assess how albumin production changes along the biliary tree. METHODS: Forty-five CCAs were retrospectively selected: 29 intrahepatic (15 small-duct and 14 large-duct subtypes), 7 perihilar, and 9 extrahepatic. Histology was revised in all cases, and albumin ISH was automatically performed by the RNAscope®. RESULTS: ISH was always negative in extrahepatic CCAs, only 1 perihilar case was positive, and any positivity was observed in 25/29 (86.2%) intrahepatic CCAs (p < 0.001). Concerning CCA subtypes, mean cell positivity was 38.8 ± 29.8% in small-duct CCAs and 11.4 ± 21.9 in large-duct CCAs, respectively (p = 0.003); 12/15 (80.0%) small-duct and 3/14 (21.4%) large-duct CCAs showed >5% positive cells (p = 0.002; odds ratio 14.7). CONCLUSIONS: The introduction of more sensitive techniques changed the indications for ISH since most small-duct intrahepatic CCAs show diffuse positivity. Albumin positivity decreases from liver periphery to the large ducts, suggesting that ISH can be helpful in the differential diagnosis between small-duct and large-duct CCAs, as well as between intrahepatic large-duct CCAs and metastases.

Validation of the Italian version of the Myasthenia Gravis Impairment Index (MGII).

OBJECTIVE: To validate the Italian version of the Myasthenia Gravis Impairment Index (MGII). INTRODUCTION: MGII is a recent promising measure developed for MG patient evaluation. It includes a clinical severity evaluation and a patient-reported questionnaire. It has been developed in English and has demonstrated feasibility, reliability, and construct validity. Recently, its Dutch translation has been validated. METHODS: MGII was translated to Italian with a multi-step forward process. We assessed correlations with the following scores: Istituto Nazionale Carlo Besta score for Myasthenia Gravis (INCB-MG), the MG Activities of Daily Living (MG-ADL), the Myasthenia Gravis Composite (MGC), the Quality of Life 15 for Myasthenia Gravis (QOL15-MG), and the Myasthenia Gravis Disability (MGDIS). We also assessed differences in MGII scores by disease severity with the ANOVA Kruskal-Wallis test. RESULTS: One hundred forty-one patients were enrolled. The mean MGII total score was 13.3 ± 11.9 (range 0-49), with a mean ocular subscore of 3.7 ± 4.7 and a mean MGII generalized subscore of 9.6 ± 9.0. As expected, the MGII had a good correlation with the other severity scores. The MGII had a lower floor effect (3.5%) than the other measures. Twenty-five patients were assessed in follow-up; as expected, the MGII change scores had moderate correlations with change in other MG severity measures and lower correlations with quality of life measures. CONCLUSIONS: The MGII score was cross-culturally validated in an Italian cohort of MG patients. We confirmed its lower floor effect and the correlations with other MG measures including INCB-MG that was not evaluated in previous studies.

Effect of biscuits formulated with high-amylose maize flour on satiety-related sensations and food intake.

The amount of amylose within a food may elicit lower glycemic and insulin postprandial responses and thus potentially modulate the satiating effect. In this context, the effect of biscuits formulated with high amylose starch (HAS) flour on satiety-related sensations and food intake was studied. Three types of biscuits were produced: control biscuit (CRT, 0% of HAS), Amy-25 (25% HAS), and Amy-50 (50% HAS). Fifteen healthy volunteers were enrolled to conduct two in vivo experiments. In experiment 1, volunteers consumed biscuits ad libitum and their sensations of satiety and food intake were evaluated. In experiment 2, volunteers received a quantity of biscuits equivalent to the 20% of the daily estimated energy requirements, and both satiety-related sensations and food intake were checked at subsequent meal. The Amy-50 significantly reduced food intake at subsequent meal (p ˂ 0.05), compared to Amy-25 and CRT. The satiety-related sensations were not significantly affected in both experiments, excepted for intra-meal hunger variation induced by Amy-25 which resulted significantly higher (p ˂ 0.05) than Amy-50 and CRT. These findings support the need to reformulate carbohydrate rich foods commonly consumed in a dietary context, to provide consumers healthier alternatives to prevent and tackle obesity and related chronic diseases.

Morphologic and molecular diagnostic criteria of malignancies in biliary strictures.

The differential diagnosis of benign and malignant biliary strictures is not always feasible and still represents a major diagnostic challenge, mainly due to the scarcity of the tissue retrieved for proper cytological or histopathological diagnosis. The present review focuses on morphological criteria in the diagnosis of biliary strictures, in the course of primary sclerosing cholangitis and other pathologies, starting from the limits of the cytological and histological evaluation, as well as the ancillary methodologies currently available in Pathology laboratories The current guidelines suggest fluorescence in situ hybridization for the analysis of chromosomes 3, 7, and 17 polysomies and deletion of the 9p21 locus; however, other more promising techniques are on the horizon for both patient care and research purposes, such as Next-Generation Sequencing, able to analyze multiple genes simultaneously in a cost-effective fashion. Lastly, the most recent approaches proposed in the literature for the differential diagnosis of biliary stricture are described, such as circulating tumor DNA, miRNAs, and DNA methylation, among others.

Beyond histology: A tissue algorithm predictive of post-surgical recurrence in hepatocellular carcinomas, including TERT promoter mutation.

Surgical resection for hepatocellular carcinoma (HCC) is burdened with a high recurrence rate and a lack of reliable prognostic factors. The aim of this study was to integrate the HCC pathological features with gene mutations to improve the prognostic role of pathological analysis. This is a monocentric prospective study, including 67 patients resected for HCC. All clinical data and histological features were collected, including tumor grade, architecture, margins, microvascular invasion, and microscopic portal vascular invasion (MPVI). Next-generation sequencing (NGS) was performed using a laboratory-developed multi-gene panel, allowing to amplify 330 amplicons (21.77 kb), covering the relevant targets for solid tumor analysis. The most represented mutations were TERT promoter (n = 41, 61.2%), TP53 (n = 18, 26.9%) and CTNNB1 (n = 17, 25.4%). At follow-up, 13 (19.4%) patients experienced HCC recurrence: at multivariate analysis, tumor dimensions (p = 0.040), MPVI (p = 0.010), and TERT mutation (p = 0.034) correlated with recurrence. Dimensions ≥ 4.5 cm (very close to AJCC stage pT3; 9 recurrences, p = 0.041, odd-ratio = 3.7), MPVI (9 recurrences, p = 0.062, OR = 3.3), and TERT (11 recurrences, p = 0.049, OR = 4.4) correlated with disease-free survival also at univariate analysis. The concomitant occurrence of these three variables was present in 7 cases, among which 5 recurred (p = 0.002, OR = 15.94). In conclusion, NGS analysis in resected HCC could not only be used for future therapies but should be integrated with histopathology to predict the risk of tumor recurrence after surgical resection: TERT mutation is among the strongest predictors of tumor recurrence, together with tumor stage (dimensions) and the occurrence of MPVI, which should always be reported separately from the classic MVI.

Donors risk assessment in transplantation: From the guidelines to their real-world application.

Transplantation of an organ from a donor carries an unavoidable risk of tumor transmission. The need to extend the donor pool increases the use of organs from donors with malignancies and potential disease transmission is a constant tension influencing donor suitability decisions. Current classification systems for the assessment of donor malignancy transmission risk have evolved from reports of potential transmission events in recipients to national donation and transplant surveillance agencies. Although the risk of malignancy transmission is very low in the general transplant setting it must constantly be balanced with the transplant benefits. Guidelines are mainly based on large registries and sparse case reports of transmission, so they cannot cover all the possible situations. For this reason, in 2004 in Italy, the National Transplant Center gave rise to the Second Opinion Service, charged by the Ministry of Health, by structuring expertise in diagnostic oncology and risk transmission and making it available to the Italian Transplant Centers. In this paper the registry of the Italian Oncological Second Opinion was reviewed, from 2016 to 2018, to detail the most frequent and problematic neoplastic topics addressed, those are separately reported and discussed. Furthermore, a review of the most recent strategies and risk stratification is provided, according to the most recent literature evidence and to the European Guidelines.

State-of-the-art review on the correlations between pathological and magnetic resonance features of cirrhotic nodules.

Hepatocellular carcinoma (HCC) has become the second greatest cause of cancer-related mortality worldwide and the newest advancements in liver imaging have improved the diagnosis of both overt malignancies and premalignant lesions, such as cirrhotic or dysplastic nodules, which is crucial to improve overall patient survival rate and to choose the best treatment options. The role of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) has grown in the last 20 years. In particular, the introduction of hepatospecific contrast agents has strongly increased the definition of precursor nodules and detection of high-grade dysplastic nodules and early HCCs. Nevertheless, the diagnosis of liver tumours in cirrhotic patients sometimes remains challenging for radiologists, thus, in doubtful cases, biopsy and histological analysis become critical in clinical practice. This current review briefly summarizes the history of imaging and histology for HCC, covering the newest techniques and their limits. Then, the article discusses the links between radiological and pathological characteristics of liver lesions in cirrhotic patients, by describing the multistep process of hepatocarcinogenesis. Explaining the evolution of pathologic change from cirrhotic nodules to malignancy, the list of analyzed lesions provides regenerative nodules, low-grade and high-grade dysplastic nodules, small HCC and progressed HCC, including common subtypes (steatohepatitic HCC, scirrhous HCC, macrotrabecular massive HCC) and more rare forms (clear cell HCC, chromophobe HCC, neutrophil-rich HCC, lymphocyte-rich HCC, fibrolamellar HCC). The last chapter covers the importance of the new integrated morphological-molecular classification and its association with radiological features.

Locoregional Treatments in Cholangiocarcinoma and Combined Hepatocellular Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a primary and aggressive cancer of the biliary tree. Combined hepatocellular cholangiocarcinoma (CHC) is a distinctive primary liver malignancy which has properties of both hepatocytic and cholangiocytic differentiation. CHC appears to have a worse prognosis compared to hepatocellular carcinoma, and similar to that of intrahepatic CCA. While significant advances have been made in understanding the pathophysiology and treatment of these two tumor types, their prognosis remains poor. Currently, liver resection is the primary treatment modality; however, only a minority of patients are eligible for surgery. However, the use of locoregional therapies proves an alternative approach to treating locally advanced disease with the aim of converting to resectability or even transplantation. Locoregional therapies such as transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), radiofrequency ablation (RFA), and photodynamic therapy (PDT) can provide patients with tumor control and increase the chances of survival. In this review, we appraise the evidence surrounding the use of locoregional therapies in treating patients with CCA and CHC.

Psychopathological features and suicidal ideation in amyotrophic lateral sclerosis patients.

Psychopathological diagnosis has become increasingly important in amyotrophic lateral sclerosis (ALS), since the recent emphasis on the comprehensive management and end-of-life decisions. Rorschach test is the third most commonly used psychological instrument worldwide and can offer a different approach from self-reporting questionnaires, mainly providing information on issues of which individuals may be unaware or unwilling to admit to. Forty-two ALS patients underwent a psychopathological assessment with the Rorschach test. Psychopathological data were also correlated with skeletal muscle strength as measured by MRC scale and functional evaluation as ALSFRSr and FVC values. Psychopathological features, including suicidial ideation, were more frequent in the recently diagnosed ALS patients. These features were observed to be different according to the kind of functional impairment. Rorschach test may be an useful tool to assess psychopathological features in ALS. Results of our study highlight the need of an early psychopathological diagnosis and specific psychotherapeutic treatment in patients with ALS.