Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease

Background: The intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD. Methods: Thirty-one CD patients and 7 controls were enrolled. Circulating CD133+ and CD34+ HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3+ lymphoid cells) and the putative ISC compartment (CD133+ and Lgr5+ epithelial cells). Results: At enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal. Conclusions: In active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission

Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment

none94Aim: This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. Methods: 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material deprivation (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. Results: In more deprived regions, HCC was more frequently diagnosed during surveillance, while the incidental diagnosis was prevalent in the least deprived. Tumour characteristics did not differ among regions. The proportion of patients undergoing potentially curative treatments progressively decreased as the SMD worsened. Consequently, overall survival was better in less deprived regions. Patients who moved from most deprived to less deprived regions increased their probability of receiving potentially curative treatments by 1.11 times (95% CI 1.03 to 1.19), decreasing their mortality likelihood (hazard ratio 0.78 95% CI 0.67 to 0.90). Conclusions: Socioeconomic status measured through SMD does not seem to influence HCC features at diagnosis but brings a negative effect on the chance of receiving potentially curative treatments. Patient mobility from the most deprived to the less deprived regions increased the access to curative therapies, with the ultimate result of improving survival.openCucchetti A.; Gramenzi A.; Johnson P.; Giannini E.G.; Tovoli F.; Rapaccini G.L.; Marra F.; Cabibbo G.; Caturelli E.; Gasbarrini A.; Svegliati-Baroni G.; Sacco R.; Zoli M.; Morisco F.; Di Marco M.; Mega A.; Foschi F.G.; Biasini E.; Masotto A.; Nardone G.; Raimondo G.; Azzaroli F.; Vidili G.; Brunetto M.R.; Farinati F.; Trevisani F.; Avanzato F.; Biselli M.; Caraceni P.; Garuti F.; Neri A.; Santi V.; Pellizzaro F.; Imondi A.; Sartori A.; Penzo B.; Sanmarco A.; Granito A.; Muratori L.; Piscaglia F.; Sansone V.; Forgione A.; Dajti E.; Marasco G.; Ravaioli F.; Cappelli A.; Golfieri R.; Mosconi C.; Renzulli M.; Cela E.M.; Facciorusso A.; Cacciato V.; Casagrande E.; Moscatelli A.; Pellegatta G.; de Matthaeis N.; Allegrini G.; Lauria V.; Ghittoni G.; Pelecca G.; Chegai F.; Coratella F.; Ortenzi M.; Missale G.; Olivani A.; Inno A.; Marchetti F.; Busacca A.; Camma C.; Di Martino V.; Maria Rizzo G.E.; Franze M.S.; Saitta C.; Sauchella A.; Berardinelli D.; Bevilacqua V.; Borghi A.; Gardini A.C.; Conti F.; Dall'Aglio A.C.; Ercolani G.; Adotti V.; Arena U.; Di Bonaventura C.; Campani C.; Dragoni G.; Gitto S.; Laffi G.; Coccoli P.; Malerba A.; Guarino M.; Capasso M.; Oliveri F.; Romagnoli V.Cucchetti, A.; Gramenzi, A.; Johnson, P.; Giannini, E. G.; Tovoli, F.; Rapaccini, G. L.; Marra, F.; Cabibbo, G.; Caturelli, E.; Gasbarrini, A.; Svegliati-Baroni, G.; Sacco, R.; Zoli, M.; Morisco, F.; Di Marco, M.; Mega, A.; Foschi, F. G.; Biasini, E.; Masotto, A.; Nardone, G.; Raimondo, G.; Azzaroli, F.; Vidili, G.; Brunetto, M. R.; Farinati, F.; Trevisani, F.; Avanzato, F.; Biselli, M.; Caraceni, P.; Garuti, F.; Neri, A.; Santi, V.; Pellizzaro, F.; Imondi, A.; Sartori, A.; Penzo, B.; Sanmarco, A.; Granito, A.; Muratori, L.; Piscaglia, F.; Sansone, V.; Forgione, A.; Dajti, E.; Marasco, G.; Ravaioli, F.; Cappelli, A.; Golfieri, R.; Mosconi, C.; Renzulli, M.; Cela, E. M.; Facciorusso, A.; Cacciato, V.; Casagrande, E.; Moscatelli, A.; Pellegatta, G.; de Matthaeis, N.; Allegrini, G.; Lauria, V.; Ghittoni, G.; Pelecca, G.; Chegai, F.; Coratella, F.; Ortenzi, M.; Missale, G.; Olivani, A.; Inno, A.; Marchetti, F.; Busacca, A.; Camma, C.; Di Martino, V.; Maria Rizzo, G. E.; Franze, M. S.; Saitta, C.; Sauchella, A.; Berardinelli, D.; Bevilacqua, V.; Borghi, A.; Gardini, A. C.; Conti, F.; Dall'Aglio, A. C.; Ercolani, G.; Adotti, V.; Arena, U.; Di Bonaventura, C.; Campani, C.; Dragoni, G.; Gitto, S.; Laffi, G.; Coccoli, P.; Malerba, A.; Guarino, M.; Capasso, M.; Oliveri, F.; Romagnoli, V

Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: A pilot case-control study

Background:Limited therapies are available for large ( 6540 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods: Eighty-two patients with a single HCC nodule 6540 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively (p &lt; 0.001). Subsequently we stratified the HCCs in 3 categories according to the nodule size: 40-50 mm, 51-60 mm, and &gt; 60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively (p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions: LA is a more effective therapeutic option than TACE in patients with solitary large HCC

Expression of ECM proteins fibulin-1 and -2 in acute and chronic liver disease and in cultured rat liver cells

Fibulin-2 has previously been considered as a marker to distinguish rat liver myofibroblasts from hepatic stellate cells. The function of other fibulins in acute or chronic liver damage has not yet been investigated. The aim of this study has been to evaluate the expression of fibulin-1 and -2 in models of rat liver injury and in human liver cirrhosis. Their cellular sources have also been investigated. In normal rat liver, fibulin-1 and -2 were both mainly present in the portal field. Fibulin-1-coding transcripts were detected in total RNA of normal rat liver, whereas fibulin-2 mRNA was only detected by sensitive, real-time quantitative polymerase chain reaction. In acute liver injury, the expression of fibulin-1 was significantly increased (17.23-fold after 48 h), whereas that of fibulin-2 was not modified. The expression of both fibulin-1 and -2 was increased in experimental rat liver cirrhosis (19.16- and 26.47-fold, respectively). At the cellular level, fibulin-1 was detectable in hepatocytes, “activated” hepatic stellate cells, and liver myofibroblasts (2.71-, 122.65-, and 469.48-fold over the expression in normal rat liver), whereas fibulin-2 was restricted to liver myofibroblasts and was regulated by transforming growth factor beta-1 (TGF-β1) in 2-day-old hepatocyte cultures and in liver myofibroblasts. Thus, fibulin-1 and -2 respond differentially to single and repeated damaging noxae, and their expression is differently present in liver cells. Expression of the fibulin-2 gene is regulated by TGF-β1 in liver myofibroblasts

Accuracy of VirtualTouch Acoustic Radiation Force Impulse (ARFI) Imaging for the Diagnosis of Cirrhosis during Liver Ultrasonography

PURPOSE: VirtualTouch is a new technique recently proposed to evaluate liver stiffness during B-mode ultrasonography. The goal of the present study was to analyze the diagnostic accuracy of VirtualTouch in the diagnosis of cirrhosis and its correlation with transient elastography (Fibroscan). MATERIALS AND METHODS: A total of 133 patients with chronic liver disease were enrolled. 90 of 133 underwent VirtualTouch and transient elastography and 70 patients assessed with VirtualTouch were submitted to liver biopsy. Stiffness was assessed by both techniques in the right liver lobe. The diagnostic accuracy for cirrhosis was first assessed in the 90 patients submitted to transient elastography with > 13 kPa (47 % of patients) as diagnostic for cirrhosis values. The best cut-off for cirrhosis with VirtualTouch was then tested in the 70 patients with biopsy (cirrhosis in 38 % of patients). 41 patients were assessed by VirtualTouch by two different operators. RESULTS: The VirtualTouch values in controls, chronic hepatitis and cirrhosis were respectively 113, 147 and 255 cm/sec. The AUROC of liver VirtualTouch for the diagnosis of cirrhosis (reference Fibroscan) was 0.941 with 175 cm/sec as the best cut-off (sensitivity 93.0 %; specificity 85.1 %). VirtualTouch confirmed good performance also in patients with bioptic diagnosis of cirrhosis (AUROC 0.908, sensitivity 81.5 %, specificity 88.4 %,). The correlation of VirtualTouch with transient elastography was strict (r = 0.891) and the correlation in VirtualTouch measurements between two operators was also good (r = 0.874). CONCLUSION: VirtualTouch is able to identify the presence of cirrhosis with good accuracy, shows good interobserver reproducibility and the correlation of its values with those obtained by transient elastography with Fibroscan is good