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1. Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis

Author

Italian PBC Genetics Study Group, Seldin, Mf, Gershwin, Me, Podda, M, de Bakker PI, Cusi, D, Siminovitch, Ka, Gregersen, Pk, Amos, Ci, Bossa, F, Franke, A, Shigeta, R, Lleo, A, Kosoy, R, Raychaudhuri, S, Ransom, M, Invernizzi, P, Almasio, Pl, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, Mc, Brunetto, M, Bruno, S, Caliari, L, Casella, G, Civardi, F, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Croce, Ls, Crosignani, A, Donato, F, Fabris, L, Ferrari, C, Floreani, A, Galli, A, Grattagliano, I, Lazzari, R, Macaluso, F, Marra, F, Marzioni, M, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Moroni, L, Muratori, L, Muratori, P, Niro, G, Picciotto, A, Portincasa, P, Prati, D, Prisco, C, Rosina, F, Rossi, S, Selmi, C, Spinzi, G, Strazzabosco, M, Tarallo, S, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M., Invernizzi P, Ransom M, Raychaudhuri S, Kosoy R, Lleo A, Shigeta R, Franke A, Bossa F, Amos CI, Gregersen PK, Siminovitch KA, Cusi D, de Bakker PI, Podda M, Gershwin ME, Seldin MFAlmasio PL, Alvaro D, Andreone P, Andriulli A, Barlassina C, Benedetti A, Bernuzzi F, Bianchi I, Bragazzi MC, Brunetto M, Bruno S, Caliari L, Casella G, Civardi F, Coco B, Colli A, Colombo M, Colombo S, Cursaro C, Croce LS, Crosignani A, Donato F, Fabris L, Ferrari C, Floreani A, Galli A, Grattagliano I, Lazzari R, Macaluso F, Marra F, Marzioni M, Mattalia A, Montanari R, Morini L, Morisco F, Moroni L, Muratori L, Muratori P, Niro G, Picciotto A, Portincasa P, Prati D, Prisco C, Rosina F, Rossi S, Selmi C, Spinzi G, Strazzabosco M, Tarallo S, Tiribelli C, Toniutto P, Vinci M, Zuin M., Invernizzi, P., Ransom, M., Raychaudhuri, S., Kosoy, R., Lleo, A., Shigeta, R., Franke, A, Bossa, F., Amos, Ci, Gregersen, Pk, Siminovitch, Ka, Cusi, D., de Bakker, Pi, Podda, M, Gershwin, Me, Seldin, Mf, The Italian PBC Genetics Study, Group, Croce', Saveria, Tiribelli, Claudio, Invernizzi, P, Ransom, M, Raychaudhuri, S, Kosoy, R, Lleo, A, Shigeta, R, Bossa, F, Cusi, D, Morisco, Filomena, Italian PBC Genetics Study, Group, Amos, C, Gregersen, P, Siminovitch, K, de Bakker, P, Gershwin, M, Seldin, M, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, M, Brunetto, M, Bruno, S, Caliari, L, Casella, G, Civardi, F, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Croce, L, Crosignani, A, Donato, F, Fabris, L, Ferrari, C, Floreani, A, Galli, A, Grattagliano, I, Lazzari, R, Macaluso, F, Marra, F, Marzioni, M, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Moroni, L, Muratori, L, Muratori, P, Niro, G, Picciotto, A, Portincasa, P, Prati, D, Prisco, C, Rosina, F, Rossi, S, Selmi, C, Spinzi, G, Strazzabosco, M, Tarallo, S, Tiribelli, C, Toniutto, P, Vinci, M, and Zuin, M

Subjects
AUTOIMMUNITY, PRIMARY BILIARY CIRRHOSIS, genetic risk, imputation, 0302 clinical medicine, Primary biliary cirrhosis, Gene Frequency, MED/12 - GASTROENTEROLOGIA, immune system diseases, Risk Factors, Genetic risk, skin and connective tissue diseases, HLA-DRB1, Genetics (clinical), HLA-DP beta-Chains, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, Liver Cirrhosis, Biliary, antigen binding pocket, Italy, HLA-DRB1 Chain, 030211 gastroenterology & hepatology, Case-Control Studie, antigen-binding pocket, Human, musculoskeletal diseases, risk allele, European Continental Ancestry Group, Immunology, Autoimmune Diseases, autoimmune disease, Biology, Polymorphism, Single Nucleotide, White People, Article, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, Allele, 030304 developmental biology, Autoimmune disease, Oligonucleotide Array Sequence Analysi, Risk Factor, HLA polymorfism, PBC, HLA-DRB1, HLA-DPB1, Hla association, medicine.disease, HLA-DP beta-Chain, Case-Control Studies, Risk allele, Imputation (genetics), Genome-Wide Association Study, HLA-DRB1 Chains
Abstract

Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (P=1.59 × 10(-11)) was the strongest predisposing allele, whereas DRB1*11 (P=1.42 × 10(-10)) was protective. Additionally, DRB1*14 and the DPB1 association (DPB1*03:01; P=9.18 × 10(-7)) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC.Genes and Immunity advance online publication, 10 May 2012; doi:10.1038/gene.2012.17.

Published
2012

2. Pathway-based analysis of primary biliary cirrhosis genome-wide association studies

Author

Kar, Sp, Seldin, Mf, Chen, W, Lu, E, Hirschfield, Gm, Invernizzi, P, Heathcote, J, Cusi, D, Almasio, Pl, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, M, Brunetto, M, Bruno, S, Caliari, L, Casella, G, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Croce, Ls, Crosignani, A, Donato, F, Elia, G, Fabris, L, Floreani, A, Galli, A, Grattagliano, I, Lazzari, R, Lleo, A, Macaluso, F, Marra, F, Marzioni, M, Mascia, E, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, Picciotto, A, Podda, M, Portincasa, P, Prati, D, Raggi, C, Rosina, F, Rossi, S, Sogno, I, Spinzi, G, Strazzabosco, M, Tarallo, Sonia, Tarocchi, M, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, Gershwin, Me, Siminovitch, Ka, Amos, Ci, Tarallo, S, Zuin, M., S. P., Kar, M. F., Seldin, W., Chen, E., Lu, G. M., Hirschfield, P., Invernizzi, J., Heathcote, D., Cusi, t. I., Pbc, P. L., Almasio, D., Alvaro, P., Andreone, A., Andriulli, C., Barlassina, A., Benedetti, F., Bernuzzi, I., Bianchi, M., Bragazzi, M., Brunetto, S., Bruno, L., Caliari, G., Casella, B., Coco, A., Colli, M., Colombo, S., Colombo, C., Cursaro, Croce', Saveria, A., Crosignani, F., Donato, G., Elia, L., Fabri, A., Floreani, A., Galli, I., Grattagliano, R., Lazzari, A., Lleo, F., Macaluso, F., Marra, M., Marzioni, E., Mascia, A., Mattalia, R., Montanari, L., Morini, F., Morisco, L., Muratori, P., Muratori, G., Niro, A., Picciotto, M., Podda, P., Portincasa, D., Prati, C., Raggi, F., Rosina, S., Rossi, I., Sogno, G., Spinzi, M., Strazzabosco, S., Tarallo, M., Tarocchi, Tiribelli, Claudio, P., Toniutto, M., Vinci, M., Zuin, M. E., Gershwin, K. A., Siminovitch, C. I., Amos, SP Kar, MF Seldin, W Chen, E Lu, GM Hirschfield, P Invernizzi, J Heathcote, D Cusi, the Italian PBC Genetics Study Group [.., P Andreone, L Muratori, P Muratori, ], ME Gershwin, KA Siminovitch, CI Amos, Kar, S, Seldin, M, Chen, W, Lu, E, Hirschfield, G, Invernizzi, P, Heathcote, J, Cusi, D, the Italian PBC Genetics Study, G, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, M, Brunetto, M, Bruno, S, Caliari, L, Casella, G, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Croce, L, Crosignani, A, Donato, F, Elia, G, Fabris, L, Floreani, A, Galli, A, Grattagliano, I, Lazzari, R, Lleo, A, Macaluso, F, Marra, F, Marzioni, M, Mascia, E, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G., P, A, Podda, M, Portincasa, P, Prati, D, Raggi, C, Rosina, F, Rossi, S, Sogno, I, Spinzi, G, Strazzabosco, M, Tarallo, S, Tarocchi, M, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, Gershwin, M, Siminovitch, K, Amos, C, Kar, Sp, Seldin, Mf, Hirschfield, Gm, Almasio, Pl, Morisco, Filomena, Niro, G, Picciotto, A, Gershwin, Me, Siminovitch, Ka, Amos, Ci, and the Italian PBC Genetics Study, Group

Subjects
Male, Linkage disequilibrium, PRIMARY BILIARY CIRRHOSIS, Genome-wide association study, VARIANTS, Linkage Disequilibrium, Cohort Studies, ACTIVATION, Primary biliary cirrhosis, Gene Frequency, MED/12 - GASTROENTEROLOGIA, Databases, Genetic, SENSORS, Genetics (clinical), Genetics, Liver Cirrhosis, Biliary, Middle Aged, EPITHELIAL-MESENCHYMAL TRANSITION, hedgehog signaling, Hedgehog signaling pathway, Algorithm, Italy, DISEASES, Female, Algorithms, TRAITS, Human, Signal Transduction, Canada, Genotype, Immunology, EPITHELIAL-MESENCHYMAL TRANSITION, CELLS, ACTIVATION, GENE, IDENTIFICATION, RESPONSES, VARIANTS, DISEASES, SENSORS, TRAITS, autoimmune disease, Biology, Polymorphism, Single Nucleotide, linear combination test, Article, Autoimmune Diseases, Meta-Analysis as Topic, medicine, Humans, Genetic Predisposition to Disease, phosphatidylinositol signaling, KEGG, Allele frequency, Genetic association, IDENTIFICATION, medicine.disease, GENE, Multiple comparisons problem, PBC, genome wide association, CELLS, Cohort Studie, Genome-Wide Association Study, RESPONSES
Abstract

Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P

Published
2013

4. Pathway-based analysis of primary biliary cirrhosis genome-wide association studies

Author

Kar, S, Seldin, M, Chen, W, Lu, E, Hirschfield, G, Invernizzi, P, Heathcote, J, Cusi, D, the Italian PBC Genetics Study, G, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, M, Brunetto, M, Bruno, S, Caliari, L, Casella, G, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Croce, L, Crosignani, A, Donato, F, Elia, G, Fabris, L, Floreani, A, Galli, A, Grattagliano, I, Lazzari, R, Lleo, A, Macaluso, F, Marra, F, Marzioni, M, Mascia, E, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G., P, A, Podda, M, Portincasa, P, Prati, D, Raggi, C, Rosina, F, Rossi, S, Sogno, I, Spinzi, G, Strazzabosco, M, Tarallo, S, Tarocchi, M, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, Gershwin, M, Siminovitch, K, Amos, C, Kar, SP, Seldin, MF, Hirschfield, GM, INVERNIZZI, PIETRO, the Italian PBC Genetics Study Group, Almasio, PL, Bernuzzi, Francesca Veronica, Croce, LS, G. Picciotto, STRAZZABOSCO, MARIO, Gershwin, ME, Siminovitch, KA, Amos, CI, Kar, S, Seldin, M, Chen, W, Lu, E, Hirschfield, G, Invernizzi, P, Heathcote, J, Cusi, D, the Italian PBC Genetics Study, G, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, M, Brunetto, M, Bruno, S, Caliari, L, Casella, G, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Croce, L, Crosignani, A, Donato, F, Elia, G, Fabris, L, Floreani, A, Galli, A, Grattagliano, I, Lazzari, R, Lleo, A, Macaluso, F, Marra, F, Marzioni, M, Mascia, E, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G., P, A, Podda, M, Portincasa, P, Prati, D, Raggi, C, Rosina, F, Rossi, S, Sogno, I, Spinzi, G, Strazzabosco, M, Tarallo, S, Tarocchi, M, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, Gershwin, M, Siminovitch, K, Amos, C, Kar, SP, Seldin, MF, Hirschfield, GM, INVERNIZZI, PIETRO, the Italian PBC Genetics Study Group, Almasio, PL, Bernuzzi, Francesca Veronica, Croce, LS, G. Picciotto, STRAZZABOSCO, MARIO, Gershwin, ME, Siminovitch, KA, and Amos, CI

Abstract

Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P<0.05). After correcting for multiple comparisons, only the eight most significant pathways in the Italian dataset had FDR <0.25 with tumor necrosis factor/stress-related signaling emerging as the top pathway (P=7.38 × 10(-4), FDR=0.18). Two pathways, phosphatidylinositol signaling and hedgehog signaling, were replicated in both datasets (P<0.05), and subjected to two additional complementary pathway tests. Both pathway signals remained significant in the Italian dataset on modified gene set enrichment analysis (P<0.05). In both GWAS, variants nominally associated with PBC were significantly overrepresented in the phosphatidylinositol pathway (Fisher exact P<0.05). These results point to established and novel pathway-level associations with inherited predisposition to PBC that, on further independent replication and functional validation, may provide fresh insights into PBC etiology

Published
2013

5. Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis

Author

Invernizzi, P, Ransom, M, Raychaudhuri, S, Kosoy, R, Lleo, A, Shigeta, R, Franke, A, Bossa, F, Amos, C, Gregersen, P, Siminovitch, K, Cusi, D, de Bakker, P, Podda, M, Gershwin, M, Seldin, M, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, M, Brunetto, M, Bruno, S, Caliari, L, Casella, G, Civardi, F, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Croce, L, Crosignani, A, Donato, F, Fabris, L, Ferrari, C, Floreani, A, Galli, A, Grattagliano, I, Lazzari, R, Macaluso, F, Marra, F, Marzioni, M, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Moroni, L, Muratori, L, Muratori, P, Niro, G, Picciotto, A, Portincasa, P, Prati, D, Prisco, C, Rosina, F, Rossi, S, Selmi, C, Spinzi, G, Strazzabosco, M, Tarallo, S, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, INVERNIZZI, PIETRO, Amos, CI, Gregersen, PK, Siminovitch, KA, de Bakker, PI, Gershwin, ME, Seldin, MF, Almasio, PL, Bernuzzi, Francesca Veronica, Bragazzi, MC, Croce, LS, STRAZZABOSCO, MARIO, Zuin, M., Invernizzi, P, Ransom, M, Raychaudhuri, S, Kosoy, R, Lleo, A, Shigeta, R, Franke, A, Bossa, F, Amos, C, Gregersen, P, Siminovitch, K, Cusi, D, de Bakker, P, Podda, M, Gershwin, M, Seldin, M, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, M, Brunetto, M, Bruno, S, Caliari, L, Casella, G, Civardi, F, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Croce, L, Crosignani, A, Donato, F, Fabris, L, Ferrari, C, Floreani, A, Galli, A, Grattagliano, I, Lazzari, R, Macaluso, F, Marra, F, Marzioni, M, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Moroni, L, Muratori, L, Muratori, P, Niro, G, Picciotto, A, Portincasa, P, Prati, D, Prisco, C, Rosina, F, Rossi, S, Selmi, C, Spinzi, G, Strazzabosco, M, Tarallo, S, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, INVERNIZZI, PIETRO, Amos, CI, Gregersen, PK, Siminovitch, KA, de Bakker, PI, Gershwin, ME, Seldin, MF, Almasio, PL, Bernuzzi, Francesca Veronica, Bragazzi, MC, Croce, LS, STRAZZABOSCO, MARIO, and Zuin, M.

Abstract

Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (P=1.59 × 10(-11)) was the strongest predisposing allele, whereas DRB1*11 (P=1.42 × 10(-10)) was protective. Additionally, DRB1*14 and the DPB1 association (DPB1*03:01; P=9.18 × 10(-7)) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC.

Published
2012

6. Bariatric surgery drives major rearrangements of the intestinal microbiota including the biofilm composition.

Author

Campisciano G, Cason C, Palmisano S, Giuricin M, Rizzardi A, Croce LS, De Manzini N, and Comar M

Subjects
Biofilms, Case-Control Studies, Humans, Obesity surgery, Prospective Studies, Gastric Bypass, Gastrointestinal Microbiome, Intestinal Mucosa microbiology, Obesity microbiology
Abstract

The intestinal microbiota disequilibrium has been associated with obesity, while the role of the gut mucosal biofilms in this pathology is still unknown. We analysed the changes in the intestinal microbiota of obese patients after bariatric surgery with the aim of disclosing the rearrangement of the biofilm configuration. Although the bariatric surgery drives major rearrangements of the gut microbiota, obese patients maintain the Prevotella enterotype before and after surgery, as shown by normal weight patients, with an increase of Bacteroides vulgatus and Bacteroides uniformis . The Bacteroides enterotype guarantees the strong ability to form a biofilm which allows a more efficient digestion of polysaccharides than planktonic communities and leads to the production of acetate which is a key player to inhibit enteropathogens. Additionally, the laparoscopic gastric bypass induces an increase of Hafnia alvei (Proteobacteria) , a facultative anaerobic bacterium involved in intestinal and inflammatory disorders. Bariatric surgery influences the microbial composition of gut biofilm. Further studies are needed to elucidate the impact of this variation on recovery after surgery and on weight loss.

Published
2018
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7. Treatment options in Western hepatocellular carcinoma: a prospective study of 224 patients.

Author

Markovic S, Gadzijev E, Stabuc B, Croce LS, Masutti F, Surlan M, Berden P, Brencic E, Visnar-Perovic A, Sasso F, Ferlan-Marolt V, Mucelli FP, Cesar R, Sponza M, and Tiribelli C

Subjects
Aged, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Female, Humans, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Prospective Studies, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic adverse effects, Liver Neoplasms therapy
Abstract

Background/aims: Though hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world, the optimal therapeutic strategy is still poorly defined. This is mainly due to geographic differences in HCC which may affect the validity of treatment regimens in differents areas of the world. The aim of the present study was to analyze the natural course of the disease as well as to assess the efficacy of different therapeutical schemes in HCC observed in Ljubljana (Slovenia) and Trieste (Italy), two cities in Western Europe situated close to each other., Methods: During the period from January 1988 to December 1993, 224 consecutive patients (132 in Trieste and 92 in Ljubljana) with HCC were enrolled in the study. Patients were treated with the following 3 schemes: surgery 39 (17.4%), transcatheter chemoembolization (TACE) 116 (51.8%), and no treatment 69 (30.8%). The tumor was classified by Okuda staging and the liver disease by Child-Pugh score. Patients were followed up for 12-60 months, with an average of 40 months. The response rate to TACE and recurrence following surgery were evaluated. Comparative analysis of survival between different treatment groups was performed., Results: The natural course of the disease, and other characteristics of the HCC, showed a typical Western type of tumor. Liver disease was scored as Child A in 58%, Child B in 30% and Child C in 12%, and the tumor was staged as Okuda I in 52%, Okuda II in 37% and Okuda III in 11%, respectively. Treatment with TACE was followed by an objective response in 27%, with a median survival of 31 months. Surgery was followed by a recurrence rate of 77% within 19.5 months and median survival of 49 months. The overall median survival of nontreated patients was 8 months. Survival in each group of patients differed significantly between all three consecutive stages of Okuda (p<0.001). In contrast, the differences in survival were significant only between Child A and B (p<0.02). The differences between Child B and C were not significant., Conclusions: This study emphasizes the importance of staging in the choice of treatment modality and diffusion of HCC in affecting an overall response to treatment and survival. Surgery is highly effective in monofocal HCC of Okuda I and II without cirrhosis. TACE is effective in Okuda I and II and Child A cirrhosis only. The treatment of HCC in Child B cirrhosis needs further studies. In Child C and/or Okuda stage III of HCC, any treatment except pure symptomatic relief is detrimental and should not be used.

Published
1998
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8. Incidence of hepatocellular carcinoma in Italy: what could we learn from autoptic studies?

Author

Tiribelli C, Croce LS, Polo S, Sodde M, and Stanta G

Subjects
Adult, Aged, Aged, 80 and over, Autopsy, Carcinoma, Hepatocellular complications, Chronic Disease, Female, Humans, Incidence, Italy epidemiology, Liver Cirrhosis complications, Liver Diseases complications, Liver Neoplasms complications, Male, Middle Aged, Carcinoma, Hepatocellular epidemiology, Liver Neoplasms epidemiology
Abstract

From January 1, 1968 to December 31, 1984, 31,955 autopsies were performed at the Department of Pathology of the University of Trieste. Of these 16,521 were male and 15,434 female which covered about 70% of the population who died in the area over the recent years. Hepatocellular carcinoma (HCC) associated with liver cirrhosis was encountered in 441 cases (380 males and 61 females, M:F ratio 5.8:1) with an overall occurrence of 1.4% in the autoptic population. On the contrary and in the absence of chronic liver disease HCC was only observed in 0.3% of the cases (45 males and 16 females, M:F ratio 2.7:1). Liver cirrhosis accounted for 10% of autopsies (2099 males and 1104 females, M:F ratio 1.8:1). A 15% of cirrhosis was associated with HCC, indicating that major attention should be paid to cirrhotic patients, in particular males after the 5th decade of life. The year distribution of HCC and cirrhosis was fairly constant during the period of time considered. These data suggest that: i) HCC is common in Italy; ii) in the vast majority, HCC occurs in the presence of cirrhosis; and iii) HCC appears to be a rather late disease as it does not reduce the life expectancy of cirrhotic and control populations. Since reliable, nationwide epidemiological data are not available in Italy, it is not known whether these data represent a local realty or whether they may be extrapolated to the entire country. Cooperative and prospective studies appear appropriate in investigating possible geographical differences in HCC distribution and permit a better understanding and prevention of the disease.

Published
1991

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