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1. Preoperative prediction of post hepatectomy liver failure after surgery for hepatocellular carcinoma on CT-scan by machine learning and radiomics analyses

Author

Famularo, Simone, Maino, Cesare, Milana, Flavio, Ardito, Francesco, Rompianesi, Gianluca, Ciulli, Cristina, Conci, Simone, Gallotti, Anna, La Barba, Giuliano, Romano, Maurizio, De Angelis, Michela, Patauner, Stefan, Penzo, Camilla, De Rose, Agostino Maria, Marescaux, Jacques, Diana, Michele, Ippolito, Davide, Frena, Antonio, Boccia, Luigi, Zanus, Giacomo, Ercolani, Giorgio, Maestri, Marcello, Grazi, Gian Luca, Ruzzenente, Andrea, Romano, Fabrizio, Troisi, Roberto Ivan, Giuliante, Felice, Donadon, Matteo, and Torzilli, Guido

Published
2024
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4. The Italian Consensus on minimally invasive simultaneous resections for synchronous liver metastasis and primary colorectal cancer: A Delphi methodology

Author

Rocca, Aldo, Cipriani, Federica, Belli, Giulio, Berti, Stefano, Boggi, Ugo, Bottino, Vincenzo, Cillo, Umberto, Cescon, Matteo, Cimino, Matteo, Corcione, Francesco, De Carlis, Luciano, Degiuli, Maurizio, De Paolis, Paolo, De Rose, Agostino Maria, D’Ugo, Domenico, Di Benedetto, Fabrizio, Elmore, Ugo, Ercolani, Giorgio, Ettorre, Giuseppe M., Ferrero, Alessandro, Filauro, Marco, Giuliante, Felice, Gruttadauria, Salvatore, Guglielmi, Alfredo, Izzo, Francesco, Jovine, Elio, Laurenzi, Andrea, Marchegiani, Francesco, Marini, Pierluigi, Massani, Marco, Mazzaferro, Vincenzo, Mineccia, Michela, Minni, Francesco, Muratore, Andrea, Nicosia, Simone, Pellicci, Riccardo, Rosati, Riccardo, Russolillo, Nadia, Spinelli, Antonino, Spolverato, Gaya, Torzilli, Guido, Vennarecci, Giovanni, Viganò, Luca, Vincenti, Leonardo, Delrio, Paolo, Calise, Fulvio, and Aldrighetti, Luca

Published
2021
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12. DCLK1, a putative novel stem cell marker in human cholangiocarcinoma

Author

Safarikia Samira, Monti Marco, Grazi Gian Luca, Caretti Giuseppina, Bosco Daniela, De Peppo Valerio, Invernizzi Pietro, Bragazzi Maria Consiglia, Ambrosino Valeria, Di Matteo Sabina, Zizzari Ilaria Grazia, Overi Diletta, Massironi Sara, Giuliante Felice, Oddi Andrea, Cardinale Vincenzo, Giancotti Antonella, Gaudio Eugenio, Melandro Fabio, Panici P. Benedetti, Berloco Paquale Bartomeo, Carpino Guido, Nevi Lorenzo, Faccioli Jessica, De Rose Agostino Maria, Costantini Daniele, Alvaro Domenico, Nevi, L, Di Matteo, S, Carpino, G, Zizzari, I, Safarikia, S, Ambrosino, V, Costantini, D, Overi, D, Giancotti, A, Monti, M, Bosco, D, De Peppo, V, Oddi, A, De Rose, A, Melandro, F, Bragazzi, M, Faccioli, J, Massironi, S, Grazi, G, Panici, P, Berloco, P, Giuliante, F, Cardinale, V, Invernizzi, P, Caretti, G, Gaudio, E, and Alvaro, D

Subjects
0301 basic medicine, Cell, Cancer Stem Cell, Protein Serine-Threonine Kinases, Stem cell marker, Receptors, G-Protein-Coupled, NO, Cholangiocarcinoma, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Doublecortin-Like Kinases, Cancer stem cell, Cell Line, Tumor, Cancer Stem Cells, medicine, Biomarkers, Tumor, Hepatobiliary Malignancies, Humans, LS4_6, Cell Proliferation, Invasivene, Biomarker, DCAMKL1, Invasiveness, Primary liver cancer, Hepatology, Cluster of differentiation, Chemistry, Cell growth, LGR5, Intracellular Signaling Peptides and Proteins, Epithelial cell adhesion molecule, Original Articles, Molecular biology, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, Bile Duct Neoplasms, Cell culture, Neoplastic Stem Cells, Original Article, 030211 gastroenterology & hepatology, Erratum
Abstract

Background and aims Cholangiocarcinoma (CCA) is a very aggressive cancer showing the presence of high cancer stem cells (CSCs). Doublecortin-like kinase1 (DCLK1) has been demonstrated as a CSC marker in different gastroenterological solid tumors. Our aim was to evaluate in vitro the expression and the biological function of DCLK1 in intrahepatic CCA (iCCA) and perihilar CCA (pCCA). Approach and results Specimens surgically resected of human CCA were enzymatically digested, submitted to immunosorting for specific CSC markers (LGR5 [leucine-rich repeat-containing G protein-coupled receptor], CD [clusters of differentiation] 90, EpCAM [epithelial cell adhesion molecule], CD133, and CD13), and primary cell cultures were prepared. DCLK1 expression was analyzed in CCA cell cultures by real-time quantitative PCR, western blot, and immunofluorescence. Functional studies have been performed by evaluating the effects of selective DCLK1 inhibitor (LRRK2-IN-1) on cell proliferation (MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, cell population doubling time), apoptosis, and colony formation capacity. DCLK1 was investigated in situ by immunohistochemistry and real-time quantitative PCR. DCLK1 serum concentration was analyzed by enzyme-linked immunosorbent assay. We describe DCLK1 in CCA with an increased gene and protein DCLK1 expression in pCCALGR5+ and in iCCACD133+ cells compared with unsorted cells. LRRK2-IN-1 showed an anti-proliferative effect in a dose-dependent manner. LRRK2-IN-1 markedly impaired cell proliferation, induced apoptosis, and decreased colony formation capacity and colony size in both iCCA and pCCA compared with the untreated cells. In situ analysis confirmed that DCLK1 is present only in tumors, and not in healthy tissue. Interestingly, DCLK1 was detected in the human serum samples of patients with iCCA (high), pCCA (high), HCC (low), and cirrhosis (low), but it was almost undetectable in healthy controls. Conclusions DCLK1 characterizes a specific CSC subpopulation of iCCACD133+ and pCCALGR5+ , and its inhibition exerts anti-neoplastic effects in primary CCA cell cultures. Human DCLK1 serum might represent a serum biomarker for the early CCA diagnosis.

Published
2021

15. Erratum: Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles (Cell Reports (2017) 18(11) (2780–2794) (S2211124717302140) (10.1016/j.celrep.2017.02.033))

Author

Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A. Gordon, Hinoue, Toshinori, Hoadley, Katherine A., Gibb, Ewan A., Roszik, Jason, Covington, Kyle R., Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I., Hess, Julian M., Auman, J. Todd, Rhie, Suhn K., Bowlby, Reanne, Borad, Mitesh J., Akbani, Rehan, Allotey, Loretta K., Ally, Adrian, Alvaro, Domenico, Andersen, Jesper B., Appelbaum, Elizabeth L., Arora, Arshi, Balasundaram, Miruna, Balu, Saianand, Bardeesy, Nabeel, Bathe, Oliver F., Baylin, Stephen B., Beroukhim, Rameen, Berrios, Mario, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bowen, Jay, Bragazzi, Maria Consiglia, Brooks, Denise, Cardinale, Vincenzo, Carlsen, Rebecca, Carpino, Guido, Carvalho, Andre L., Chaiteerakij, Roongruedee, Chandan, Vishal C., Cherniack, Andrew D., Chin, Lynda, Cho, Juok, Choe, Gina, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cordes, Matthew G., Crain, Daniel, Curley, Erin, De Rose, Agostino Maria, Defreitas, Timothy, Demchok, John A., Deshpande, Vikram, Dhalla, Noreen, Ding, Li, Evason, Kimberley, Felau, Ina, Ferguson, Martin L., Foo, Wai Chin, Franchitto, Antonio, Frazer, Scott, Fronick, Catrina C., Fulton, Lucinda A., Fulton, Robert S., Gabriel, Stacey B., Gardner, Johanna, Gastier-Foster, Julie M., Gaudio, Eugenio, Gehlenborg, Nils, Genovese, Giannicola, Gerken, Mark, Getz, Gad, Giama, Nasra H., Gibbs, Richard A., Giuliante, Felice, Grazi, Gian Luca, Hayes, D. Neil, Hegde, Apurva M., Heiman, David I., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Huang, Mei, Hutter, Carolyn M., Jefferys, Stuart R., Jones, Steven J. M., Jones, Corbin D., Kasaian, Katayoon, Kelley, Robin K., Kim, Jaegil, Kleiner, David E., Kocher, Jean-Pierre A., Kwong, Lawrence N., Lai, Phillip H., Laird, Peter W., Lawrence, Michael S., Leraas, Kristen M., Lichtenberg, Tara M., Lin, Pei, Liu, Wenbin, Liu, Jia, Lolla, Laxmi, Lu, Yiling, Ma, Yussanne, Mallery, David, Mardis, Elaine R., Marra, Marco A., Matsushita, Marcus M., Mayo, Michael, McLellan, Michael D., McRee, Autumn J., Meier, Sam, Meng, Shaowu, Meyerson, Matthew, Mieczkowski, Piotr A., Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morris, Scott, Mose, Lisle E., Moser, Catherine D., Mounajjed, Taofic, Mungall, Andrew J., Mungall, Karen, Murray, Bradley A., Naresh, Rashi, Noble, Michael S., O'Brien, Daniel R., Parker, Joel S., Patel, Tushar C., Paulauskis, Joseph, Penny, Robert, Perou, Charles M., Perou, Amy H., Pihl, Todd, Radenbaugh, Amie J., Ramirez, Nilsa C., Rathmell, W. Kimryn, Roach, Jeffrey, Roberts, Lewis R., Saksena, Gordon, Sander, Chris, Schein, Jacqueline E., Schmidt, Heather K., Schumacher, Steven E., Shelton, Candace, Shelton, Troy, Shen, Ronglai, Sheth, Margi, Shi, Yan, Shroff, Rachna, Simons, Janae V., Sipahimalani, Payal, Skelly, Tara, Sofia, Heidi J., Soloway, Matthew G., Stoppler, Hubert, Stuart, Josh, Sun, Qiang, Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thorne, Leigh B., Torbenson, Michael S., Van Den Berg, David J., Veluvolu, Umadevi, Verhaak, Roel G. W., Voet, Doug, Wan, Yunhu, Wang, Zhining, Weinstein, John N., Weisenberger, Daniel J., Wheeler, David A., Wilson, Richard K., Wise, Lisa, Wong, Tina, Wu, Ye, Xi, Liu, Yang, Liming, Zenklusen, Jean C., Zhang, Hailei, Zhang, Jiashan (Julia), Zmuda, Erik, Zhu, Andrew X., Stuart, Josh M., Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A. Gordon, Hinoue, Toshinori, Hoadley, Katherine A., Gibb, Ewan A., Roszik, Jason, Covington, Kyle R., Chia-Chin, Wu, Shinbrot, Eve, Stransky, Nicola, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I., Hess, Julian M., Auman, J. Todd, Rhie, Suhn K., Bowlby, Reanne, Borad, Mitesh J., Akbani, Rehan, Allotey, Loretta K., Ally, Adrian, Alvaro, Domenico, Andersen, Jesper B., Appelbaum, Elizabeth L., Arora, Arshi, Balasundaram, Miruna, Balu, Saianand, Bardeesy, Nabeel, Bathe, Oliver F., Baylin, Stephen B., Beroukhim, Rameen, Berrios, Mario, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bowen, Jay, Bragazzi, Maria Consiglia, Brooks, Denise, Cardinale, Vincenzo, Carlsen, Rebecca, Guido, Carpino, Carvalho, Andre L., Chaiteerakij, Roongruedee, Chandan, Vishal C., Cherniack, Andrew D., Chin, Lynda, Cho, Juok, Choe, Gina, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cordes, Matthew G., Crain, Daniel, Curley, Erin, De Rose, Agostino Maria, Defreitas, Timothy, Demchok, John A., Deshpande, Vikram, Dhalla, Noreen, Ding, Li, Evason, Kimberley, Felau, Ina, Ferguson, Martin L., Foo, Wai Chin, Franchitto, Antonio, Frazer, Scott, Fronick, Catrina C., Fulton, Lucinda A., Fulton, Robert S., Gabriel, Stacey B., Gardner, Johanna, Gastier-Foster, Julie M., Gaudio, Eugenio, Gehlenborg, Nil, Genovese, Giannicola, Gerken, Mark, Getz, Gad, Giama, Nasra H., Gibbs, Richard A., Giuliante, Felice, Grazi, Gian Luca, Hayes, D. Neil, Hegde, Apurva M., Heiman, David I., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Huang, Mei, Hutter, Carolyn M., Jefferys, Stuart R., Jones, Steven J. M., Jones, Corbin D., Kasaian, Katayoon, Kelley, Robin K., Kim, Jaegil, Kleiner, David E., Kocher, Jean-Pierre A., Kwong, Lawrence N., Lai, Phillip H., Laird, Peter W., Lawrence, Michael S., Leraas, Kristen M., Lichtenberg, Tara M., Lin, Pei, Liu, Wenbin, Liu, Jia, Lolla, Laxmi, Yiling, Lu, Yussanne, Ma, Mallery, David, Mardis, Elaine R., Marra, Marco A., Matsushita, Marcus M., Mayo, Michael, Mclellan, Michael D., Mcree, Autumn J., Meier, Sam, Meng, Shaowu, Meyerson, Matthew, Mieczkowski, Piotr A., Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morris, Scott, Mose, Lisle E., Moser, Catherine D., Mounajjed, Taofic, Mungall, Andrew J., Mungall, Karen, Murray, Bradley A., Naresh, Rashi, Noble, Michael S., O'Brien, Daniel R., Parker, Joel S., Patel, Tushar C., Paulauskis, Joseph, Penny, Robert, Perou, Charles M., Perou, Amy H., Pihl, Todd, Radenbaugh, Amie J., Ramirez, Nilsa C., Rathmell, W. Kimryn, Roach, Jeffrey, Roberts, Lewis R., Saksena, Gordon, Sander, Chri, Schein, Jacqueline E., Schmidt, Heather K., Schumacher, Steven E., Shelton, Candace, Shelton, Troy, Shen, Ronglai, Sheth, Margi, Shi, Yan, Shroff, Rachna, Simons, Janae V., Sipahimalani, Payal, Skelly, Tara, Sofia, Heidi J., Soloway, Matthew G., Stoppler, Hubert, Stuart, Josh, Sun, Qiang, Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thorne, Leigh B., Torbenson, Michael S., Van Den Berg, David J., Veluvolu, Umadevi, Verhaak, Roel G. W., Voet, Doug, Wan, Yunhu, Wang, Zhining, Weinstein, John N., Weisenberger, Daniel J., Wheeler, David A., Wilson, Richard K., Wise, Lisa, Wong, Tina, Ye, Wu, Liu, Xi, Yang, Liming, Zenklusen, Jean C., Zhang, Hailei, Zhang, Jiashan (Julia), Zmuda, Erik, Zhu, Andrew X., and Stuart, Josh M.

Subjects
Genetics and Molecular Biology (all), Biochemistry, Genetics and Molecular Biology (all), Biochemistry
Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

Published
2017

16. Parenteral Nutrition in Liver Resection

Author

Chiarla, Carlo, Giovannini, Ivo, Giuliante, Felice, Ardito, Francesco, Vellone, Maria, De Rose, Agostino Maria, and Nuzzo, Gennaro

Subjects
Article Subject
Abstract

Albeit a very large number of experiments have assessed the impact of various substrates on liver regeneration after partial hepatectomy, a limited number of clinical studies have evaluated artificial nutrition in liver resection patients. This is a peculiar topic because many patients do not need artificial nutrition, while several patients need it because of malnutrition and/or prolonged inability to feeding caused by complications. The optimal nutritional regimen to support liver regeneration, within other postoperative problems or complications, is not yet exactly defined. This short review addresses relevant aspects and potential developments in the issue of postoperative parenteral nutrition after liver resection.

Published
2012
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19. Sensitivity of Human Intrahepatic Cholangiocarcinoma Subtypes to Chemotherapeutics and Molecular Targeted Agents: A Study on Primary Cell Cultures.

Author

Fraveto, Alice, Cardinale, Vincenzo, Bragazzi, Maria Consiglia, Giuliante, Felice, De Rose, Agostino Maria, Grazi, Gian Luca, Napoletano, Chiara, Semeraro, Rossella, Lustri, Anna Maria, Costantini, Daniele, Nevi, Lorenzo, Di Matteo, Sabina, Renzi, Anastasia, Carpino, Guido, Gaudio, Eugenio, and Alvaro, Domenico

Subjects
CHOLANGIOCARCINOMA, CANCER chemotherapy, TARGETED drug delivery, CELL culture, CISPLATIN
Abstract

We investigated the sensitivity of intrahepatic cholangiocarcinoma (IHCCA) subtypes to chemotherapeutics and molecular targeted agents. Primary cultures of mucin- and mixed-IHCCA were prepared from surgical specimens (N. 18 IHCCA patients) and evaluated for cell proliferation (MTS assay) and apoptosis (Caspase 3) after incubation (72 hours) with increasing concentrations of different drugs. In vivo, subcutaneous human tumor xenografts were evaluated. Primary cultures of mucin- and mixed-IHCCA were characterized by a different pattern of expression of cancer stem cell markers, and by a different drug sensitivity. Gemcitabine and the Gemcitabine-Cisplatin combination were more active in inhibiting cell proliferation in mixed-IHCCA while Cisplatin or Abraxane were more effective against mucin-IHCCA, where Abraxane also enhances apoptosis. 5-Fluoracil showed a slight inhibitory effect on cell proliferation that was more significant in mixed- than mucin-IHCCA primary cultures and, induced apoptosis only in mucin-IHCCA. Among Hg inhibitors, LY2940680 and Vismodegib showed slight effects on proliferation of both IHCCA subtypes. The tyrosine kinase inhibitors, Imatinib Mesylate and Sorafenib showed significant inhibitory effects on proliferation of both mucin- and mixed-IHCCA. The MEK 1/2 inhibitor, Selumetinib, inhibited proliferation of only mucin-IHCCA while the aminopeptidase-N inhibitor, Bestatin was more active against mixed-IHCCA. The c-erbB2 blocking antibody was more active against mixed-IHCCA while, the Wnt inhibitor, LGK974, similarly inhibited proliferation of mucin- and mixed-IHCCA. Either mucin- or mixed-IHCCA showed high sensitivity to nanomolar concentrations of the dual PI3-kinase/mTOR inhibitor, NVP-BEZ235. In vivo, in subcutaneous xenografts, either NVP-BEZ235 or Abraxane, blocked tumor growth. In conclusion, mucin- and mixed-IHCCA are characterized by a different drug sensitivity. Cisplatin, Abraxane and the MEK 1/2 inhibitor, Selumetinib were more active against mucin-IHCCA while, Gemcitabine, Gemcitabine-Cisplatin combination, the c-erbB2 blocking antibody and bestatin worked better against mixed-IHCCA. Remarkably, we identified a dual PI3-kinase/mTOR inhibitor that both in vitro and in vivo, exerts dramatic antiproliferative effects against both mucin- and mixed-IHCCA. [ABSTRACT FROM AUTHOR]

Published
2015
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20. Investigating the Synergistic Interaction of Diabetes, Tobacco Smoking, Alcohol Consumption, and Hypercholesterolemia on the Risk of Pancreatic Cancer: A Case-Control Study in Italy.

Author

Torre, Giuseppe La, Sferrazza, Antonella, Gualano, Maria Rosaria, de Waure, Chiara, Clemente, Gennaro, De Rose, Agostino Maria, Nicolotti, Nicola, Nuzzo, Gennaro, Siliquini, Roberta, Boccia, Antonio, and Ricciardi, Walter

Abstract

The aims of the present research are to investigate the possible predictors of pancreatic cancer, in particular smoking status, alcohol consumption, hypercholesterolemia, and diabetes mellitus, in patients with histologically confirmed pancreatic carcinoma and to examine the synergism between risk factors. A case-control study (80 patients and 392 controls) was conducted at the Teaching Hospital "Agostino Gemelli" in Rome. A conditional logistic regression was used for the statistical analysis and results were presented as odds ratio (OR) and 95% confidence intervals (95% CI).We also investigated the possible interactions between risk factors and calculated the synergism index (SI). The multivariate analysis revealed that hypercholesterolemia and alcohol consumption resulted in important risk factors for pancreatic cancer even after the adjustment for all variables (OR: 5.05, 95% CI: 2.94-8.66; OR: 2.25, 95% CI: 1.30-3.89, resp.). Interestingly, important synergistic interactions between risk factors were found, especially between ever smoking status and alcohol consumptions (SI = 17.61) as well as alcohol consumption and diabetes (SI = 17.77). In conclusion, the study confirms that hypercholesterolemia and alcohol consumption represent significant and independent risk factors for pancreatic cancer. Moreover, there is evidence of synergistic interaction between diabetes and lifestyle factors (drinking alcohol and eating fatty foods). 1. [ABSTRACT FROM AUTHOR]

Published
2014
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21. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Author

Kasaian, Katayoon, Veluvolu, Umadevi, Berrios, Mario, Kleiner, David E., Tan, Donghui, Gardner, Johanna, Cherniack, Andrew D., Bowlby, Reanne, Shinbrot, Eve, Parker, Joel S., Deshpande, Vikram, Mungall, Andrew J., O’Brien, Daniel R., Farshidfar, Farshad, Laird, Peter W., Yang, Ju Dong, Jones, Steven J.M., Roach, Jeffrey, Chandan, Vishal C., Foo, Wai Chin, Weinstein, John N., Liu, Wenbin, Ojesina, Akinyemi I., Hinoue, Toshinori, Perou, Amy H., Wu, Chia-Chin, Leraas, Kristen M., Auman, J. Todd, Arora, Arshi, Lai, Phillip H., Skelly, Tara, Zenklusen, Jean C., Holbrook, Andrea, Giama, Nasra H., Wang, Zhining, Mills, Gordon B., Gibbs, Richard A., Zmuda, Erik, Reznik, Ed, Demchok, John A., Xi, Liu, Wu, Ye, Tam, Angela, Hegde, Apurva M., Chuah, Eric, Stoppler, Hubert, Covington, Kyle R., Bowen, Jay, Carpino, Guido, Robertson, A. Gordon, Zhu, Andrew X., Hayes, D. Neil, Pihl, Todd, Cordes, Matthew G., Naresh, Rashi, Cardinale, Vincenzo, Huang, Mei, Rathmell, W. Kimryn, Gingras, Marie-Claude, Mayo, Michael, Zhang, Jiashan (Julia), Shen, Ronglai, Bathe, Oliver F., Wheeler, David A., Ma, Yussanne, Patel, Tushar C., Murray, Bradley A., Fulton, Lucinda A., Matsushita, Marcus M., Chaiteerakij, Roongruedee, Crain, Daniel, Wilson, Richard K., Shelton, Candace, Schumacher, Steven E., Moore, Richard A., Gaudio, Eugenio, Paulauskis, Joseph, De Rose, Agostino Maria, Carvalho, Andre L., Roberts, Lewis R., Lawrence, Michael S., Wong, Tina, Bardeesy, Nabeel, Mallery, David, Chin, Lynda, Soloway, Matthew G., Simons, Janae V., Bodenheimer, Tom, Jones, Corbin D., Morris, Scott, Genovese, Giannicola, Kim, Jaegil, Andersen, Jesper B., Appelbaum, Elizabeth L., Shroff, Rachna, Thiessen, Nina, Alvaro, Domenico, Brooks, Denise, Sun, Qiang, Schein, Jacqueline E., Sofia, Heidi J., Evason, Kimberley, Weisenberger, Daniel J., Allotey, Loretta K., Bootwalla, Moiz S., Fulton, Robert S., Marra, Marco A., Beroukhim, Rameen, Sheth, Margi, Pedamallu, Chandra Sekhar, Lu, Yiling, Boice, Lori, Hoadley, Katherine A., Noble, Michael S., Grazi, Gian Luca, Kocher, Jean-Pierre A., Ally, Adrian, Kwong, Lawrence N., Meng, Shaowu, Moser, Catherine D., Gibb, Ewan A., Hutter, Carolyn M., Zheng, Siyuan, Shi, Yan, McLellan, Michael D., Giuliante, Felice, Van Den Berg, David J., Ramirez, Nilsa C., Thorne, Leigh B., Sander, Chris, McRee, Autumn J., Bragazzi, Maria Consiglia, Getz, Gad, Mose, Lisle E., Zhang, Hailei, Ding, Li, Shih, Juliann, Tarnuzzer, Roy, Rhie, Suhn K., Meier, Sam, Baylin, Stephen B., Cho, Juok, Miller, Christopher A., Felau, Ina, Mieczkowski, Piotr A., Shelton, Troy, Cibulskis, Carrie, Schmidt, Heather K., Borad, Mitesh J., Balu, Saianand, Jefferys, Stuart R., Ferguson, Martin L., Saksena, Gordon, Mardis, Elaine R., Sadeghi, Sara, Hoyle, Alan P., Frazer, Scott, Stransky, Nicolas, Carlsen, Rebecca, Roszik, Jason, Wan, Yunhu, Defreitas, Timothy, Mounajjed, Taofic, Fronick, Catrina C., Balasundaram, Miruna, Gabriel, Stacey B., Penny, Robert, Yang, Liming, Newton, Yulia, Perou, Charles M., Lin, Pei, Holt, Robert A., Chudamani, Sudha, Radenbaugh, Amie J., Mungall, Karen, Stuart, Josh, Kelley, Robin K., Curley, Erin, Lolla, Laxmi, Verhaak, Roel G.W., Liu, Jia, Dhalla, Noreen, Heiman, David I., Gehlenborg, Nils, Choe, Gina, Wise, Lisa, Gerken, Mark, Franchitto, Antonio, Gastier-Foster, Julie M., Lichtenberg, Tara M., Akbani, Rehan, Hess, Julian M., Torbenson, Michael S., Meyerson, Matthew, Voet, Doug, and Sipahimalani, Payal

Subjects
3. Good health
Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

24. The Italian Consensus on minimally invasive simultaneous resections for synchronous liver metastasis and primary colorectal cancer: A Delphi methodology

Author

Antonino Spinelli, Gaya Spolverato, Ugo Elmore, S. Berti, Giorgio Ercolani, Nadia Russolillo, Ugo Boggi, L. Vincenti, Simone Nicosia, Andrea Laurenzi, Paolo De Paolis, Giuseppe Maria Ettorre, Agostino Maria De Rose, Luca Aldrighetti, Giovanni Vennarecci, Pierluigi Marini, Matteo Cescon, Michela Mineccia, Umberto Cillo, Francesco Marchegiani, Aldo Rocca, Francesco Minni, Luciano De Carlis, Alfredo Guglielmi, Paolo Delrio, Salvatore Gruttadauria, Riccardo Rosati, Francesco Izzo, Domenico D'Ugo, Vincenzo Bottino, Maurizio Degiuli, Giulio Belli, Fulvio Calise, Vincenzo Mazzaferro, Luca Viganò, Francesco Corcione, Fabrizio Di Benedetto, Riccardo Pellicci, Marco Filauro, Alessandro Ferrero, Andrea Muratore, Marco Massani, Federica Cipriani, Guido Torzilli, Matteo Cimino, Felice Giuliante, Elio Jovine, Rocca, A, Cipriani, F, Belli, G, Berti, S, Boggi, U, Bottino, V, Cillo, U, Cescon, M, Cimino, M, Corcione, F, De Carlis, L, Degiuli, M, De Paolis, P, De Rose, A, D'Ugo, D, Di Benedetto, F, Elmore, U, Ercolani, G, Ettorre, G, Ferrero, A, Filauro, M, Giuliante, F, Gruttadauria, S, Guglielmi, A, Izzo, F, Jovine, E, Laurenzi, A, Marchegiani, F, Marini, P, Massani, M, Mazzaferro, V, Mineccia, M, Minni, F, Muratore, A, Nicosia, S, Pellicci, R, Rosati, R, Russolillo, N, Spinelli, A, Spolverato, G, Torzilli, G, Vennarecci, G, Vigano, L, Vincenti, L, Delrio, P, Calise, F, Aldrighetti, L, Rocca, Aldo, Cipriani, Federica, Belli, Giulio, Berti, Stefano, Boggi, Ugo, Bottino, Vincenzo, Cillo, Umberto, Cescon, Matteo, Cimino, Matteo, Corcione, Francesco, De Carlis, Luciano, Degiuli, Maurizio, De Paolis, Paolo, De Rose, Agostino Maria, D’Ugo, Domenico, Di Benedetto, Fabrizio, Elmore, Ugo, Ercolani, Giorgio, Ettorre, Giuseppe M., Ferrero, Alessandro, Filauro, Marco, Giuliante, Felice, Gruttadauria, Salvatore, Guglielmi, Alfredo, Izzo, Francesco, Jovine, Elio, Laurenzi, Andrea, Marchegiani, Francesco, Marini, Pierluigi, Massani, Marco, Mazzaferro, Vincenzo, Mineccia, Michela, Minni, Francesco, Muratore, Andrea, Nicosia, Simone, Pellicci, Riccardo, Rosati, Riccardo, Russolillo, Nadia, Spinelli, Antonino, Spolverato, Gaya, Torzilli, Guido, Vennarecci, Giovanni, Viganò, Luca, Vincenti, Leonardo, Delrio, Paolo, Calise, Fulvio, Aldrighetti, Luca, Rocca A., Cipriani F., Belli G., Berti S., Boggi U., Bottino V., Cillo U., Cescon M., Cimino M., Corcione F., De Carlis L., Degiuli M., De Paolis P., De Rose A.M., D'Ugo D., Di Benedetto F., Elmore U., Ercolani G., Ettorre G.M., Ferrero A., Filauro M., Giuliante F., Gruttadauria S., Guglielmi A., Izzo F., Jovine E., Laurenzi A., Marchegiani F., Marini P., Massani M., Mazzaferro V., Mineccia M., Minni F., Muratore A., Nicosia S., Pellicci R., Rosati R., Russolillo N., Spinelli A., Spolverato G., Torzilli G., Vennarecci G., Vigano L., Vincenti L., Delrio P., Calise F., and Aldrighetti L.

Subjects
Synchronous colorectal liver metastases, medicine.medical_specialty, Consensus, Colorectal cancer, Delphi method, Consensu, Colorectal Neoplasm, 030230 surgery, law.invention, Metastasis, Standard procedure, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Minimally invasive surgery, medicine, Hepatectomy, Humans, Italy, Colorectal Neoplasms, Liver Neoplasms, computer.programming_language, business.industry, General surgery, medicine.disease, Chemotherapy regimen, Surgery, Systematic review, 030220 oncology & carcinogenesis, business, computer, Delphi, Synchronous colorectal liver metastase, Human
Abstract

At the time of diagnosis synchronous colorectal cancer, liver metastases (SCRLM) account for 15–25% of patients. If primary tumour and synchronous liver metastases are resectable, good results may be achieved performing surgical treatment incorporated into the chemotherapy regimen. So far, the possibility of simultaneous minimally invasive (MI) surgery for SCRLM has not been extensively investigated. The Italian surgical community has captured the need and undertaken the effort to establish a National Consensus on this topic. Four main areas of interest have been analysed: patients’ selection, procedures, techniques, and implementations. To establish consensus, an adapted Delphi method was used through as many reiterative rounds were needed. Systematic literature reviews were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses instructions. The Consensus took place between February 2019 and July 2020. Twenty-six Italian centres participated. Eighteen clinically relevant items were identified. After a total of three Delphi rounds, 30-tree recommendations reached expert consensus establishing the herein presented guidelines. The Italian Consensus on MI surgery for SCRLM indicates possible pathways to optimise the treatment for these patients as consensus papers express a trend that is likely to become shortly a standard procedure for clinical pictures still on debate. As matter of fact, no RCT or relevant case series on simultaneous treatment of SCRLM are available in the literature to suggest guidelines. It remains to be investigated whether the MI technique for the simultaneous treatment of SCRLM maintain the already documented benefit of the two separate surgeries.

Published
2021

25. Evaluation of the economic impact of the robotic approach in major and postero-superior segment liver resections: a multicenter retrospective analysis.

Author

Ingallinella S, Ardito F, Ratti F, Marino R, Catena M, De Rose AM, Razionale F, Rumi F, Cicchetti A, Giuliante F, and Aldrighetti L

Abstract

Background: Economic impact of robotic liver surgery (RLS) is still a debated issue due to the heterogeneity of liver resections considered and the lack of a rigorous methodology. Therefore, the aim of this study is to perform a time-driven activity-based costing (TD-ABC) comparing the costs of RLS, laparoscopic liver surgery (LLS) and open liver surgery (OLS) in the context of complex liver resections and to compare short term perioperative outcomes., Methods: The institutional databases of two Italian high volume hepatobiliary centres were retrospectively reviewed from February 2021 to April 2022. Patients submitted to major hepatectomies or postero-superior liver resections were selected and divided into three groups according to the approach scheduled (RLS, LLS and OLS) and compared. Major contributors of perioperative expenses were calculated using the TD-ABC model and accurately quantifying each unit resource consumed per patient and the time spent performing each activity. A primary intention-to-treat analysis (ITT-A) including conversions in the RLS and LLS groups was performed., Results: Forty-seven RLS, 101 LLS and 124 OLS were collected. LLS and RLS showed reduced blood loss, morbidity, mortality and hospital stay compared with open. A trend towards reduced conversion rate in RLS compared to LLS was registered. Total costs associated with RLS were estimated at €10,637 vs. €9,543 for LLS and vs. €13,960 for OLS. The higher intraoperative costs associated with RLS (+153.3% vs. OLS and +148.2% vs. LLS, P<0.001), primarily related to surgical equipment expenses, were slightly offset by the postoperative savings (-56.0% vs. OLS and -29.4% vs. LLS, P<0.001) resulting from significantly reduced hospital stays., Conclusions: RLS offers economic advantages over OLS, as initial higher costs are offset by better perioperative outcomes. The evolving robotic marketplace is expected to drive down RLS costs, promoting widespread adoption in minimally invasive procedures. Despite its higher costs than LLS, RLS's ability to enhance minimally invasive feasibility makes it a preferred choice for complex cases, reducing the need for conversions., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-407/coif). L.A. serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare., (2024 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Published
2024
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26. Solitary fibrous tumor of the liver with Doege-Potter syndrome: An exceptional finding. Discovering the role of blood glucose levels and insulin growth factor II.

Author

Taliente F, De Rose AM, Ardito F, and Giuliante F

Subjects
Humans, Blood Glucose, Liver, Intercellular Signaling Peptides and Proteins, Solitary Fibrous Tumors, Insulins
Abstract

Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Published
2022
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27. DCLK1, a Putative Stem Cell Marker in Human Cholangiocarcinoma.

Author

Nevi L, Di Matteo S, Carpino G, Zizzari IG, Samira S, Ambrosino V, Costantini D, Overi D, Giancotti A, Monti M, Bosco D, De Peppo V, Oddi A, De Rose AM, Melandro, Bragazzi MC, Faccioli J, Massironi S, Grazi GL, Panici PB, Berloco PB, Giuliante F, Cardinale V, Invernizzi P, Caretti G, Gaudio E, and Alvaro D

Subjects
Bile Duct Neoplasms pathology, Biomarkers, Tumor genetics, Cell Line, Tumor, Cell Proliferation, Cholangiocarcinoma pathology, Doublecortin-Like Kinases, Gene Expression Regulation, Neoplastic, Humans, Intracellular Signaling Peptides and Proteins genetics, Neoplastic Stem Cells pathology, Protein Serine-Threonine Kinases genetics, Receptors, G-Protein-Coupled genetics, Bile Duct Neoplasms genetics, Biomarkers, Tumor biosynthesis, Cholangiocarcinoma genetics, Intracellular Signaling Peptides and Proteins biosynthesis, Protein Serine-Threonine Kinases biosynthesis, Receptors, G-Protein-Coupled biosynthesis
Abstract

Background and Aims: Cholangiocarcinoma (CCA) is a very aggressive cancer showing the presence of high cancer stem cells (CSCs). Doublecortin-like kinase1 (DCLK1) has been demonstrated as a CSC marker in different gastroenterological solid tumors. Our aim was to evaluate in vitro the expression and the biological function of DCLK1 in intrahepatic CCA (iCCA) and perihilar CCA (pCCA)., Approach and Results: Specimens surgically resected of human CCA were enzymatically digested, submitted to immunosorting for specific CSC markers (LGR5 [leucine-rich repeat-containing G protein-coupled receptor], CD [clusters of differentiation] 90, EpCAM [epithelial cell adhesion molecule], CD133, and CD13), and primary cell cultures were prepared. DCLK1 expression was analyzed in CCA cell cultures by real-time quantitative PCR, western blot, and immunofluorescence. Functional studies have been performed by evaluating the effects of selective DCLK1 inhibitor (LRRK2-IN-1) on cell proliferation (MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, cell population doubling time), apoptosis, and colony formation capacity. DCLK1 was investigated in situ by immunohistochemistry and real-time quantitative PCR. DCLK1 serum concentration was analyzed by enzyme-linked immunosorbent assay. We describe DCLK1 in CCA with an increased gene and protein DCLK1 expression in pCCA LGR5+ and in iCCA CD133+ cells compared with unsorted cells. LRRK2-IN-1 showed an anti-proliferative effect in a dose-dependent manner. LRRK2-IN-1 markedly impaired cell proliferation, induced apoptosis, and decreased colony formation capacity and colony size in both iCCA and pCCA compared with the untreated cells. In situ analysis confirmed that DCLK1 is present only in tumors, and not in healthy tissue. Interestingly, DCLK1 was detected in the human serum samples of patients with iCCA (high), pCCA (high), HCC (low), and cirrhosis (low), but it was almost undetectable in healthy controls., Conclusions: DCLK1 characterizes a specific CSC subpopulation of iCCA CD133+ and pCCA LGR5+ , and its inhibition exerts anti-neoplastic effects in primary CCA cell cultures. Human DCLK1 serum might represent a serum biomarker for the early CCA diagnosis., (© 2020 by the American Association for the Study of Liver Diseases.)

Published
2021
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28. Metabolic consequences of the occlusion of the main pancreatic duct with acrylic glue after pancreaticoduodenectomy.

Author

Mezza T, Clemente G, Sorice GP, Conte C, De Rose AM, Sun VA, Cefalo CM, Pontecorvi A, Nuzzo G, and Giaccari A

Subjects
Aged, Common Bile Duct Neoplasms metabolism, Common Bile Duct Neoplasms surgery, Duodenal Neoplasms metabolism, Duodenal Neoplasms surgery, Female, Humans, Insulin Resistance, Insulin Secretion, Male, Middle Aged, Retrospective Studies, Blood Glucose metabolism, Cyanoacrylates therapeutic use, Insulin metabolism, Pancreatic Ducts, Pancreaticoduodenectomy adverse effects, Pancreaticojejunostomy adverse effects
Abstract

Background: Pancreaticoduodenectomy represents the major treatment for pancreatic and periampullary neoplasms. Complications related to pancreaticojejunostomy are still the leading cause of morbidity and mortality. A solution proposed by some surgeons is the occlusion of main pancreatic duct by acrylic glue, avoiding pancreaticojejunostomy. Nevertheless, the consequences of this procedure on glucose metabolism are not well-defined., Methods: We retrospectively analyzed a cohort of 50 patients who underwent pancreaticoduodenectomy and had metabolic assessments available. The metabolic evaluation included the following: body composition and clinical evaluation, an oral glucose tolerance test, and an hyperinsulinemic euglycemic clamp procedure., Results: Twenty-three patients underwent pancreatic duct occlusion and were compared with 27 patients, well-matched controls, who underwent pancreaticojejunostomy. Pancreatic duct occlusion leads to a greater impairment in insulin secretion compared with classic pancreaticojeunostomy., Conclusion: Pancreatic duct occlusion is associated with a greater reduction in insulin secretion but does not lead to meaningful differences in the management of patients with diabetes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Published
2015
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