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2. Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

Author

Hassan, Manal, Li, Donghui, Han, Younghun, Byun, Jinyoung, Hatia, Rikita, Long, Erping, Choi, Jiyeon, Kelley, Robin, Cleary, Sean, Lok, Anna, Bracci, Paige, Permuth, Jennifer, Bucur, Roxana, Yuan, Jian-Min, Singal, Amit, Jalal, Prasun, Ghobrial, R, Santella, Regina, Kono, Yuko, Shah, Dimpy, Nguyen, Mindie, Liu, Geoffrey, Parikh, Neehar, Kim, Richard, Wu, Hui-Chen, El-Serag, Hashem, Chang, Ping, Li, Yanan, Chun, Yun, Lee, Sunyoung, Gu, Jian, Hawk, Ernest, Sun, Ryan, Huff, Chad, Rashid, Asif, Amin, Hesham, Beretta, Laura, Wolff, Robert, Antwi, Samuel, Patt, Yehuda, Hwang, Lu-Yu, Klein, Alison, Zhang, Karen, Schmidt, Mikayla, White, Donna, Goss, John, Khaderi, Saira, Marrero, Jorge, Cigarroa, Francisco, Shah, Pankil, Kaseb, Ahmed, Roberts, Lewis, and Amos, Christopher

Subjects
Humans, Genome-Wide Association Study, Liver Neoplasms, Genetic Predisposition to Disease, Carcinoma, Hepatocellular, Male, Female, Middle Aged, North America, Case-Control Studies, Polymorphism, Single Nucleotide, Aged, Genetic Loci, White People
Abstract

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Published
2024

5. The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma.

Author

Pappas, Leontios, Baiev, Islam, Reyes, Stephanie, Bocobo, Andrea, Jain, Apurva, Spencer, Kristen, Le, Tri, Rahma, Osama, Maurer, Jordan, Stanton, Jen, Zhang, Karen, De Armas, Anaemy, Deleon, Thomas, Roth, Marc, Peters, Mary, Zhu, Andrew, Boyhen, Kylie, VanCott, Christine, Patel, Tushar, Roberts, Lewis, Lindsey, Stacie, Horick, Nora, Lennerz, Jochen, Iafrate, A, Goff, Laura, Mody, Kabir, Borad, Mitesh, Shroff, Rachna, Javle, Milind, Goyal, Lipika, and Kelley, Robin

Subjects
Humans, Young Adult, Adolescent, Middle Aged, Retrospective Studies, Cholangiocarcinoma, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Biology
Abstract

PURPOSE: Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA. METHODS: A multi-institutional cohort of patients with CCA diagnosed with intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC) was used for analysis. Retrospective chart review was conducted on patients who were 50 years old and younger (young; n = 124) and older than 50 years (older; n = 723). RESULTS: Among 1,039 patients screened, 847 patients met eligibility (72% ICC, 28% ECC). Young patients had a larger median tumor size at resection compared with older patients (4.2 v 3.6 cm; P = .048), more commonly had N1 disease (65% v 43%; P = .040), and were more likely to receive adjuvant therapy (odds ratio, 4.0; 95% CI, 1.64 to 9.74). Tumors of young patients were more likely to harbor an FGFR2 fusion, BRAF mutation, or ATM mutation (P < .05 for each). Young patients were more likely to receive palliative systemic therapy (96% v 69%; P < .001), targeted therapy (23% v 8%; P < .001), and treatment on a clinical trial (31% v 19%; P = .004). Among patients who presented with advanced disease, young patients had a higher median overall survival compared with their older counterparts (17.7 v 13.5 months; 95% CI, 12.6 to 22.6 v 11.4 to 14.8; P = .049). CONCLUSION: Young patients with CCA had more advanced disease at resection, more commonly received both adjuvant and palliative therapies, and demonstrated improved survival compared with older patients. Given the low clinical trial enrollment and poor outcomes among some AYA cancer populations, data to the contrary in CCA are highly encouraging.

Published
2023

6. Molecular profiling and treatment pattern differences between intrahepatic and extrahepatic cholangiocarcinoma.

Author

Spencer, Kristen, Pappas, Leontios, Baiev, Islam, Maurer, Jordan, Bocobo, Andrea Grace, Zhang, Karen, Jain, Apurva, De Armas, Anaemy Danner, Reyes, Stephanie, Le, Tri Minh, Rahma, Osama E, Stanton, Jennifer, DeLeon, Thomas T, Roth, Marc, Peters, Mary Linton B, Zhu, Andrew X, Lennerz, Jochen K, Iafrate, A John, Boyhen, Kylie, VanCott, Christine, Roberts, Lewis R, Lindsey, Stacie, Horick, Nora, Goff, Laura Williams, Mody, Kabir, Borad, Mitesh J, Shroff, Rachna T, Kelley, Robin Kate, Javle, Milind M, and Goyal, Lipika

Subjects
Bile Ducts, Intrahepatic, Humans, Cholangiocarcinoma, Bile Duct Neoplasms, Prognosis, Risk Factors, Retrospective Studies, Patient Safety, Liver Cancer, Digestive Diseases - (Gallbladder), Rare Diseases, Liver Disease, Clinical Trials and Supportive Activities, Cancer, Clinical Research, Digestive Diseases, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundTreatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies.MethodsThis multicenter collaboration included patients with ICC or ECC treated at 1 of 8 participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were 2-sided.ResultsAmong 1039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%) (all P

Published
2023

8. Correction: Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD)

Author

Pinto e Vairo, Filippo, Kemppainen, Jennifer L., Vitek, Carolyn R. Rohrer, Whalen, Denise A., Kolbert, Kayla J., Sikkink, Kaitlin J., Kroc, Sarah A., Kruisselbrink, Teresa, Shupe, Gabrielle F., Knudson, Alyssa K., Burke, Elizabeth M., Loftus, Elle C., Bandel, Lorelei A., Prochnow, Carri A., Mulvihill, Lindsay A., Thomas, Brittany, Gable, Dale M., Graddy, Courtney B., Garzon, Giovanna G. Moreno, Ekpoh, Idara U., Porquera, Eva M. Carmona, Fervenza, Fernando C., Hogan, Marie C., El Ters, Mireille, Warrington, Kenneth J., Davis, III, John M., Koster, Matthew J., Orandi, Amir B., Basiaga, Matthew L., Vella, Adrian, Kumar, Seema, Creo, Ana L., Lteif, Aida N., Pittock, Siobhan T., Tebben, Peter J., Abate, Ejigayehu G., Joshi, Avni Y., Ristagno, Elizabeth H., Patnaik, Mrinal S., Schimmenti, Lisa A., Dhamija, Radhika, Sabrowsky, Sonia M., Wierenga, Klaas J., Keddis, Mira T., Samadder, Niloy Jewel J., Presutti, Richard J., Robinson, Steven I., Stephens, Michael C., Roberts, Lewis R., Faubion, Jr., William A., Driscoll, Sherilyn W., Wong-Kisiel, Lily C., Selcen, Duygu, Flanagan, Eoin P., Ramanan, Vijay K., Jackson, Lauren M., Mauermann, Michelle L., Ortega, Victor E., Anderson, Sarah A., Aoudia, Stacy L., Klee, Eric W., McAllister, Tammy M., and Lazaridis, Konstantinos N.

Published
2024
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9. Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort

Author

Emiloju, Oluwadunni E., Yin, Jun, Koubek, Emily, Reid, Joel M., Borad, Mitesh J., Lou, Yanyan, Seetharam, Mahesh, Edelman, Martin J., Sausville, Edward A., Jiang, Yixing, Kaseb, Ahmed O., Posey, James A., Davis, Sarah L., Gores, Gregory J., Roberts, Lewis R., Takebe, Naoko, Schwartz, Gary K., Hendrickson, Andrea E. Wahner, Kaufmann, Scott H., Adjei, Alex A., Hubbard, Joleen M., and Costello, Brian A.

Published
2024
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10. Examining the Effectiveness of Social Media for the Dissemination of Research Evidence for Health and Social Care Practitioners: Systematic Review and Meta-Analysis

Author

Sarah Roberts-Lewis, Helen Baxter, Gill Mein, Sophia Quirke-McFarlane, Fiona J Leggat, Hannah Garner, Martha Powell, Sarah White, and Lindsay Bearne

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundSocial media use has potential to facilitate the rapid dissemination of research evidence to busy health and social care practitioners. ObjectiveThis study aims to quantitatively synthesize evidence of the between- and within-group effectiveness of social media for dissemination of research evidence to health and social care practitioners. It also compared effectiveness between different social media platforms, formats, and strategies. MethodsWe searched electronic databases for articles in English that were published between January 1, 2010, and January 10, 2023, and that evaluated social media interventions for disseminating research evidence to qualified, postregistration health and social care practitioners in measures of reach, engagement, direct dissemination, or impact. Screening, data extraction, and risk of bias assessments were carried out by at least 2 independent reviewers. Meta-analyses of standardized pooled effects were carried out for between- and within-group effectiveness of social media and comparisons between platforms, formats, and strategies. Certainty of evidence for outcomes was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. ResultsIn total, 50 mixed-quality articles that were heterogeneous in design and outcome were included (n=9, 18% were randomized controlled trials [RCTs]). Reach (measured in number of practitioners, impressions, or post views) was reported in 26 studies. Engagement (measured in likes or post interactions) was evaluated in 21 studies. Direct dissemination (measured in link clicks, article views, downloads, or altmetric attention score) was analyzed in 23 studies (8 RCTs). Impact (measured in citations or measures of thinking and practice) was reported in 13 studies. Included studies almost universally indicated effects in favor of social media interventions, although effect sizes varied. Cumulative evidence indicated moderate certainty of large and moderate between-group effects of social media interventions on direct dissemination (standardized mean difference [SMD] 0.88; P=.02) and impact (SMD 0.76; P

Published
2024
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11. Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance

Author

Calvisi, Diego F., Boulter, Luke, Vaquero, Javier, Saborowski, Anna, Fabris, Luca, Rodrigues, Pedro M., Coulouarn, Cédric, Castro, Rui E., Segatto, Oreste, Raggi, Chiara, van der Laan, Luc J. W., Carpino, Guido, Goeppert, Benjamin, Roessler, Stephanie, Kendall, Timothy J., Evert, Matthias, Gonzalez-Sanchez, Ester, Valle, Juan W., Vogel, Arndt, Bridgewater, John, Borad, Mitesh J., Gores, Gregory J., Roberts, Lewis R., Marin, Jose J. G., Andersen, Jesper B., Alvaro, Domenico, Forner, Alejandro, Banales, Jesus M., Cardinale, Vincenzo, Macias, Rocio I. R., Vicent, Silve, Chen, Xin, Braconi, Chiara, Verstegen, Monique M. A., and Fouassier, Laura

Published
2023
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12. Metabolome-wide association identifies altered metabolites and metabolic pathways in the serum of patients with cholangiocarcinoma

Author

Jackson, Linsey E., Tomlinson, Jennifer L., Alva-Ruiz, Roberto, Gregory, Lindsey A., Byeon, Seul Kee, Abdelrahman, Amro M., Mun, Dong-Gi, Grant, Caroline W., Fogarty, Zachary C., Wang, Chen, Roberts, Lewis R., Graham, Rondell P., Borad, Mitesh J., Ilyas, Sumera I., Gores, Gregory J., Pandey, Akhilesh, Athreya, Arjun P., and Smoot, Rory L.

Published
2024
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13. Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD)

Author

Pinto e Vairo, Filippo, Kemppainen, Jennifer L., Vitek, Carolyn R. Rohrer, Whalen, Denise A., Kolbert, Kayla J., Sikkink, Kaitlin J., Kroc, Sarah A., Kruisselbrink, Teresa, Shupe, Gabrielle F., Knudson, Alyssa K., Burke, Elizabeth M., Loftus, Elle C., Bandel, Lorelei A., Prochnow, Carri A., Mulvihill, Lindsay A., Thomas, Brittany, Gable, Dale M., Graddy, Courtney B., Garzon, Giovanna G. Moreno, Ekpoh, Idara U., Porquera, Eva M. Carmona, Fervenza, Fernando C., Hogan, Marie C., El Ters, Mireille, Warrington, Kenneth J., Davis, III, John M., Koster, Matthew J., Orandi, Amir B., Basiaga, Matthew L., Vella, Adrian, Kumar, Seema, Creo, Ana L., Lteif, Aida N., Pittock, Siobhan T., Tebben, Peter J., Abate, Ejigayehu G., Joshi, Avni Y., Ristagno, Elizabeth H., Patnaik, Mrinal S., Schimmenti, Lisa A., Dhamija, Radhika, Sabrowsky, Sonia M., Wierenga, Klaas J., Keddis, Mira T., Samadder, Niloy Jewel J., Presutti, Richard J., Robinson, Steven I., Stephens, Michael C., Roberts, Lewis R., Faubion, Jr., William A., Driscoll, Sherilyn W., Wong-Kisiel, Lily C., Selcen, Duygu, Flanagan, Eoin P., Ramanan, Vijay K., Jackson, Lauren M., Mauermann, Michelle L., Ortega, Victor E., Anderson, Sarah A., Aoudia, Stacy L., Klee, Eric W., McAllister, Tammy M., and Lazaridis, Konstantinos N.

Published
2023
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14. Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis

Author

Han, Younghun, Byun, Jinyoung, Zhu, Catherine, Sun, Ryan, Roh, Julia Y., Cordell, Heather J., Lee, Hyun-Sung, Shaw, Vikram R., Kang, Sung Wook, Razjouyan, Javad, Cooley, Matthew A., Hassan, Manal M., Siminovitch, Katherine A., Folseraas, Trine, Ellinghaus, David, Bergquist, Annika, Rushbrook, Simon M., Franke, Andre, Karlsen, Tom H., Lazaridis, Konstantinos N., McGlynn, Katherine A., Roberts, Lewis R., and Amos, Christopher I.

Published
2023
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15. Development of a Computer-aided Prediction Tool for Evaluating Brushing Samples of Biliary Strictures

Author

Norton, Daniel, Gleeson, Ferga, Abu Dayyeh, Barham K., Bofill-Garcia, Aliana, Chandrasekhara, Vinay, Gores, Gregory, Kipp, Benjamin, Law, Ryan J., Martin, John A., Petersen, Bret, Roberts, Lewis R., Storm, Andrew C., Vargas Valls, Eric J., Marya, Neil B., Hartley, Christopher, Powers, Patrick D., Bois, Melanie C., Kerr, Sarah E., Graham, Rondell P., and Levy, Michael J.

Published
2024
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17. Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study

Author

Razavi-Shearer, Devin, Gamkrelidze, Ivane, Pan, Calvin, Jia, Jidong, Berg, Thomas, Gray, Richard, Lim, Young-Suk, Chen, Chien-Jen, Ocama, Ponsiano, Desalegn, Hailemichael, Abbas, Zaigham, Abdallah, Ayat, Aghemo, Alessio, Ahmadbekova, Sabohat, Ahn, Sang Hoon, Aho, Inka, Akarca, Ulus, Al Masri, Nasser, Alalwan, Abduljaleel, Alavian, Seyed, Al-Busafi, Said, Aleman, Soo, Alfaleh, Faleh, Alghamdi, Abdullah, Al-Hamoudi, Waleed, Aljumah, Abdulrahman, Al-Naamani, Khalid, Al-Rifai, Ahmad, Alserkal, Yousif, Altraif, Ibrahim, Amarsanaa, Jazag, Anderson, Motswedi, Andersson, Monique, Armstrong, Paige, Asselah, Tarik, Athanasakis, Kostas, Baatarkhuu, Oidov, Ben-Ari, Ziv, Bensalem, Aicha, Bessone, Fernando, Biondi, Mia, Bizri, Abdul Rahman, Blach, Sarah, Braga, Wornei, Brandão-Mello, Carlos, Brosgart, Carol, Brown, Kimberly, Brown, Jr, Robert, Bruggmann, Philip, Brunetto, Maurizia, Buti, Maria, Cabezas, Joaquin, Casanovas, Teresa, Chae, Chungman, Chan, Henry Lik Yuen, Cheinquer, Hugo, Chen, Pei-Jer, Cheng, Kent Jason, Cheon, Myeong-Eun, Chien, Cheng-Hung, Choudhuri, Gourdas, Christensen, Peer Brehm, Chuang, Wan-Long, Chulanov, Vladimir, Cisneros, Laura, Coffin, Carla, Contreras, Fernando, Coppola, Nicola, Cornberg, Markus, Cowie, Benjamin, Cramp, Matthew, Craxi, Antonio, Crespo, Javier, Cui, Fuqiang, Cunningham, Chris, Dalgard, Olav, De Knegt, Robert, De Ledinghen, Victor, Dore, Gregory, Drazilova, Sylvia, Duberg, Ann-Sofi, Egeonu, Steve, Elbadri, Mohammed, El-Kassas, Mohamed, El-Sayed, Manal, Estes, Chris, Etzion, Ohad, Farag, Elmobashar, Ferradini, Laurent, Ferreira, Paulo, Flisiak, Robert, Forns, Xavier, Frankova, Sona, Fung, James, Gane, Edward, Garcia, Virginia, García-Samaniego, Javier, Gemilyan, Manik, Genov, Jordan, Gheorghe, Liliana, Gholam, Pierre, Gish, Robert, Goleij, Pouya, Gottfredsson, Magnus, Grebely, Jason, Gschwantler, Michael, Guingane, Nanelin Alice, Hajarizadeh, Behzad, Hamid, Saeed, Hamoudi, Waseem, Harris, Aaron, Hasan, Irsan, Hatzakis, Angelos, Hellard, Margaret, Hercun, Julian, Hernandez, Javier, Hockicková, Ivana, Hsu, Yao-Chun, Hu, Ching-Chih, Husa, Petr, Janicko, Martin, Janjua, Naveed, Jarcuska, Peter, Jaroszewicz, Jerzy, Jelev, Deian, Jeruma, Agita, Johannessen, Asgeir, Kåberg, Martin, Kaita, Kelly, Kaliaskarova, Kulpash, Kao, Jia-Horng, Kelly-Hanku, Angela, Khamis, Faryal, Khan, Aamir, Kheir, Omer, Khoudri, Ibtissam, Kondili, Loreta, Konysbekova, Aliya, Kristian, Pavol, Kwon, Jisoo, Lagging, Martin, Laleman, Wim, Lampertico, Pietro, Lavanchy, Daniel, Lázaro, Pablo, Lazarus, Jeffrey V, Lee, Alice, Lee, Mei-Hsuan, Liakina, Valentina, Lukšić, Boris, Malekzadeh, Reza, Malu, Abraham, Marinho, Rui, Mendes-Correa, Maria Cássia, Merat, Shahin, Meshesha, Berhane Redae, Midgard, Håvard, Mohamed, Rosmawati, Mokhbat, Jacques, Mooneyhan, Ellen, Moreno, Christophe, Mortgat, Laure, Müllhaupt, Beat, Musabaev, Erkin, Muyldermans, Gaëtan, Naveira, Marcelo, Negro, Francesco, Nersesov, Alexander, Nguyen, Van Thi Thuy, Ning, Qing, Njouom, Richard, Ntagirabiri, Rénovat, Nurmatov, Zuridin, Oguche, Stephen, Omuemu, Casimir, Ong, Janus, Opare-Sem, Ohene, Örmeci, Necati, Orrego, Mauricio, Osiowy, Carla, Papatheodoridis, George, Peck-Radosavljevic, Markus, Pessoa, Mário, Pham, Trang, Phillips, Richard, Pimenov, Nikolay, Pincay-Rodríguez, Loreley, Plaseska-Karanfilska, Dijana, Pop, Cora, Poustchi, Hossein, Prabdial-Sing, Nishi, Qureshi, Huma, Ramji, Alnoor, Rautiainen, Henna, Razavi-Shearer, Kathryn, Remak, William, Ribeiro, Sofia, Ridruejo, Ezequiel, Ríos-Hincapié, Cielo, Robalino, Marcia, Roberts, Lewis, Roberts, Stuart, Rodríguez, Manuel, Roulot, Dominique, Rwegasha, John, Ryder, Stephen, Sadirova, Shakhlo, Saeed, Umar, Safadi, Rifaat, Sagalova, Olga, Said, Sanaa, Salupere, Riina, Sanai, Faisal, Sanchez-Avila, Juan F, Saraswat, Vivek, Sargsyants, Narina, Sarrazin, Christoph, Sarybayeva, Gulya, Schréter, Ivan, Seguin-Devaux, Carole, Seto, Wai-Kay, Shah, Samir, Sharara, Ala, Sheikh, Mahdi, Shouval, Daniel, Sievert, William, Simojoki, Kaarlo, Simonova, Marieta, Sinn, Dong Hyun, Sonderup, Mark, Sonneveld, Milan, Spearman, C Wendy, Sperl, Jan, Stauber, Rudolf, Stedman, Catherine, Sypsa, Vana, Tacke, Frank, Tan, Soek-Siam, Tanaka, Junko, Tergast, Tammo, Terrault, Norah, Thompson, Alexander, Thompson, Peyton, Tolmane, Ieva, Tomasiewicz, Krzysztof, Tsang, Tak-Yin, Uzochukwu, Benjamin, Van Welzen, Berend, Vanwolleghem, Thomas, Vince, Adriana, Voeller, Alexis, Waheed, Yasir, Waked, Imam, Wallace, Jack, Wang, Cong, Weis, Nina, Wong, Grace, Wong, Vincent, Wu, Jaw-Ching, Yaghi, Cesar, Yesmembetov, Kakharman, Yip, Terry, Yosry, Ayman, Yu, Ming-Lung, Yuen, Man-Fung, Yurdaydin, Cihan, Zeuzem, Stefan, Zuckerman, Eli, and Razavi, Homie

Published
2023
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19. Comparison of Surgical Resection and Systemic Treatment for Hepatocellular Carcinoma with Vascular Invasion: National Cancer Database Analysis

Author

Govalan, Rajalakshmi, Lauzon, Marie, Luu, Michael, Ahn, Joseph C, Kosari, Kambiz, Todo, Tsuyoshi, Kim, Irene K, Noureddin, Mazen, Kuo, Alexander, Walid, Ayoub S, Sundaram, Vinay, Lu, Shelly C, Roberts, Lewis R, Singal, Amit G, Heimbach, Julie K, Agopian, Vatche G, Nissen, Nicholas, and Yang, Ju Dong

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Patient Safety, Cancer, Liver Cancer, Rare Diseases, Liver Disease, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Hepatocellular carcinoma, Vascular invasion, Surgical resection, Prognosis
Abstract

IntroductionSmall studies from outside of the USA suggest excellent outcomes after surgical resection for hepatocellular carcinoma (HCC) with vascular invasion. The study aims to (1) compare overall survival after surgical resection and systemic therapy among patients with HCC and vascular invasion and (2) determine factors associated with receipt of surgical resection in a US population.MethodsHCC patients with AJCC clinical TNM stage 7th T3BN0M0 diagnosed between 2010 and 2017 from the National Cancer Database were analyzed. Cox and logistic regression analyses identified factors associated with overall survival and receipt of surgical resection.ResultsOf 11,259 patients with T3BN0M0 HCC, 325 (2.9%) and 4,268 (37.9%) received surgical resection and systemic therapy, respectively. In multivariable analysis, surgical resection was associated with improved survival compared to systemic therapy (adjusted hazard ratio: 0.496, 95% confidence interval: 0.426-0.578) with a median survival of 21.4 and 8.1 months, respectively. Superiority of surgical resection was observed in noncirrhotic and cirrhotic subgroups and propensity score matching and inverse probability of treatment weighting adjusted analysis. Asians were more likely to receive surgical resection, whereas Charlson comorbidity ≥3, elevated alpha-fetoprotein, smaller tumor size, care in a community cancer program, and the South or West region were associated with a lower likelihood of surgical resection.ConclusionHCC patients with vascular invasion may benefit from surgical resection compared to systemic therapies. Demographic and clinical features of HCC patients and region and type of treating facility were associated with surgical resection versus systemic treatment.

Published
2021

20. PKCλ/ι Loss Induces Autophagy, Oxidative Phosphorylation, and NRF2 to Promote Liver Cancer Progression

Author

Kudo, Yotaro, Sugimoto, Masayuki, Arias, Esperanza, Kasashima, Hiroaki, Cordes, Thekla, Linares, Juan F, Duran, Angeles, Nakanishi, Yuki, Nakanishi, Naoko, L'Hermitte, Antoine, Campos, Alex, Senni, Nadia, Rooslid, Tarmo, Roberts, Lewis R, Cuervo, Ana Maria, Metallo, Christian M, Karin, Michael, Diaz-Meco, Maria T, and Moscat, Jorge

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Digestive Diseases, Cancer, Liver Cancer, Chronic Liver Disease and Cirrhosis, Rare Diseases, Liver Disease, 2.1 Biological and endogenous factors, Aetiology, Animals, Autophagy, Carcinoma, Hepatocellular, Cell Line, Cell Line, Tumor, Disease Progression, HEK293 Cells, Hep G2 Cells, Humans, Isoenzymes, Liver Neoplasms, Mice, Knockout, NF-E2-Related Factor 2, Oxidative Phosphorylation, Protein Kinase C, RNA Interference, NRF2, PKCζ, PKCι, PKCλ, atypical PKC, autophagy, hepatocellular carcinoma, metabolic reprogramming, oxidative phosphorylation, reactive oxygen species, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Oxidative stress plays a critical role in liver tissue damage and in hepatocellular carcinoma (HCC) initiation and progression. However, the mechanisms that regulate autophagy and metabolic reprogramming during reactive oxygen species (ROS) generation, and how ROS promote tumorigenesis, still need to be fully understood. We show that protein kinase C (PKC) λ/ι loss in hepatocytes promotes autophagy and oxidative phosphorylation. This results in ROS generation, which through NRF2 drives HCC through cell-autonomous and non-autonomous mechanisms. Although PKCλ/ι promotes tumorigenesis in oncogene-driven cancer models, emerging evidence demonstrate that it is a tumor suppressor in more complex carcinogenic processes. Consistently, PKCλ/ι levels negatively correlate with HCC histological tumor grade, establishing this kinase as a tumor suppressor in liver cancer.

Published
2020

22. Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma

Author

Haber, Philipp K., Castet, Florian, Torres-Martin, Miguel, Andreu-Oller, Carmen, Puigvehí, Marc, Miho, Maeda, Radu, Pompilia, Dufour, Jean-Francois, Verslype, Chris, Zimpel, Carolin, Marquardt, Jens U., Galle, Peter R., Vogel, Arndt, Bathon, Melanie, Meyer, Tim, Labgaa, Ismail, Digklia, Antonia, Roberts, Lewis R., Mohamed Ali, Mohamed A., Mínguez, Beatriz, Citterio, Davide, Mazzaferro, Vincenzo, Finkelmeier, Fabian, Trojan, Jörg, Özdirik, Burcin, Müller, Tobias, Schmelzle, Moritz, Bejjani, Anthony, Sung, Max W., Schwartz, Myron E., Finn, Richard S., Thung, Swan, Villanueva, Augusto, Sia, Daniela, and Llovet, Josep M.

Published
2023
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23. The Use of Social Media for Dissemination of Research Evidence to Health and Social Care Practitioners: Protocol for a Systematic Review

Author

Sarah F Roberts-Lewis, Helen A Baxter, Gill Mein, Sophia Quirke-McFarlane, Fiona J Leggat, Hannah M Garner, Martha Powell, Sarah White, and Lindsay Bearne

Subjects
Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundEffective dissemination of research to health and social care practitioners enhances clinical practice and evidence-based care. Social media use has potential to facilitate dissemination to busy practitioners. ObjectiveThis is a protocol for a systematic review that will quantitatively synthesize evidence of the effectiveness of social media, compared with no social media, for dissemination of research evidence to health and social care practitioners. Social media platforms, formats, and sharing mechanisms used for effective dissemination of research evidence will also be identified and compared. MethodsElectronic database searches (MEDLINE, PsycINFO, CINAHL, ERIC, LISTA, and OpenGrey) will be conducted from January 1, 2010, to January 10, 2023, for studies published in English. Randomized, nonrandomized, pre-post study designs or case studies evaluating the effect of social media on dissemination of research evidence to postregistration health and social care practitioners will be included. Studies that do not involve social media or dissemination or those that evaluate dissemination of nonresearch information (eg, multisource educational materials) to students or members of the public only, or without quantitative data on outcomes of interest, will be excluded. Screening will be carried out by 2 independent reviewers. Data extraction and quality assessment, using either the Cochrane tool for assessing risk of bias or the Newcastle-Ottawa Scale, will be completed by 2 independent reviewers. Outcomes of interest will be reported in 4 domains (reach, engagement, dissemination, and impact). Data synthesis will include quantitative comparisons using narrative text, tables, and figures. A meta-analysis of standardized pooled effects will be undertaken, and subgroup analyses will be applied, if appropriate. ResultsSearches and screening will be completed by the end of May 2023. Data extraction and analyses will be completed by the end of July 2023, after which findings will be synthesized and reported by the end of October 2023. ConclusionsThis systematic review will summarize the evidence for the effectiveness of social media for the dissemination of research evidence to health and social care practitioners. The limitations of the evidence may include multiple outcomes or methodological heterogeneity that limit meta-analyses, potential risk of bias in included studies, and potential publication bias. The limitations of the study design may include potential insensitivity of the electronic database search strategy. The findings from this review will inform the dissemination practice of health and care research. Trial RegistrationPROSPERO CRD42022378793; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=378793 International Registered Report Identifier (IRRID)DERR1-10.2196/45684

Published
2023
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24. Recent Developments and Therapeutic Strategies against Hepatocellular Carcinoma

Author

Yarchoan, Mark, Agarwal, Parul, Villanueva, Augusto, Rao, Shuyun, Dawson, Laura A, Karasic, Thomas, Llovet, Josep M, Finn, Richard S, Groopman, John D, El-Serag, Hashem B, Monga, Satdarshan P, Wang, Xin Wei, Karin, Michael, Schwartz, Robert E, Tanabe, Kenneth K, Roberts, Lewis R, Gunaratne, Preethi H, Tsung, Allan, Brown, Kimberly A, Lawrence, Theodore S, Salem, Riad, Singal, Amit G, Kim, Amy K, Rabiee, Atoosa, Resar, Linda, Meyer, Jeffrey, Hoshida, Yujin, He, Aiwu Ruth, Ghoshal, Kalpana, Ryan, Patrick B, Jaffee, Elizabeth M, Guha, Chandan, Mishra, Lopa, Coleman, C Norman, and Ahmed, Mansoor M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Liver Disease, Liver Cancer, Cancer, Orphan Drug, Rare Diseases, Chronic Liver Disease and Cirrhosis, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Anilides, Antibodies, Monoclonal, Humanized, Carcinoma, Hepatocellular, Chemoembolization, Therapeutic, Clinical Trials as Topic, Humans, Immunotherapy, Liver Neoplasms, Molecular Targeted Therapy, Mutation, Phenylurea Compounds, Protein Kinase Inhibitors, Pyridines, Quinolines, beta Catenin, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2-5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.

Published
2019

25. Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study

Author

Blach, Sarah, Terrault, Norah A, Tacke, Frank, Gamkrelidze, Ivane, Craxi, Antonio, Tanaka, Junko, Waked, Imam, Dore, Gregory J, Abbas, Zaigham, Abdallah, Ayat R, Abdulla, Maheeba, Aghemo, Alessio, Aho, Inka, Akarca, Ulus S, Alalwan, Abduljaleel M, Alanko Blomé, Marianne, Al-Busafi, Said A, Aleman, Soo, Alghamdi, Abdullah S, Al-Hamoudi, Waleed K, Aljumah, Abdulrahman A, Al-Naamani, Khalid, Al Serkal, Yousif M, Altraif, Ibrahim H, Anand, Anil C, Anderson, Motswedi, Andersson, Monique I, Athanasakis, Kostas, Baatarkhuu, Oidov, Bakieva, Shokhista R, Ben-Ari, Ziv, Bessone, Fernando, Biondi, Mia J, Bizri, Abdul Rahman N, Brandão-Mello, Carlos E, Brigida, Krestina, Brown, Kimberly A, Brown, Jr, Robert S, Bruggmann, Philip, Brunetto, Maurizia R, Busschots, Dana, Buti, Maria, Butsashvili, Maia, Cabezas, Joaquin, Chae, Chungman, Chaloska Ivanova, Viktorija, Chan, Henry Lik Yuen, Cheinquer, Hugo, Cheng, Kent Jason, Cheon, Myeong-Eun, Chien, Cheng-Hung, Chien, Rong-Nan, Choudhuri, Gourdas, Christensen, Peer Brehm, Chuang, Wan-Long, Chulanov, Vladimir, Cisneros, Laura E, Coco, Barbara, Contreras, Fernando A, Cornberg, Markus, Cramp, Matthew E, Crespo, Javier, Cui, Fuqiang, Cunningham, Chris W, Dagher Abou, Lucy, Dalgard, Olav, Dao, Doan Y, De Ledinghen, Victor, Derbala, Moutaz F, Deuba, Keshab, Dhindsa, Karan, Djauzi, Samsuridjal, Drazilova, Sylvia, Duberg, Ann-Sofi, Elbadri, Mohammed, El-Sayed, Manal H, Esmat, Gamal, Estes, Chris, Ezzat, Sameera, Färkkilä, Martti A, Ferradini, Laurent, Ferraz, Maria Lucia G, Ferreira, Paulo R A, Filipec Kanizaj, Tajana, Flisiak, Robert, Frankova, Sona, Fung, James, Gamkrelidze, Amiran, Gane, Edward, Garcia, Virginia, García-Samaniego, Javier, Gemilyan, Manik, Genov, Jordan, Gheorghe, Liliana S, Gholam, Pierre M, Goldis, Adrian, Gottfredsson, Magnus, Gray, Richard T, Grebely, Jason, Gschwantler, Michael, Hajarizadeh, Behzad, Hamid, Saeed S, Hamoudi, Waseem, Hatzakis, Angelos, Hellard, Margaret E, Himatt, Sayed, Hofer, Harald, Hrstic, Irena, Hunyady, Bela, Husa, Petr, Husic-Selimovic, Azra, Jafri, Wasim S M, Janicko, Martin, Janjua, Naveed, Jarcuska, Peter, Jaroszewicz, Jerzy, Jerkeman, Anna, Jeruma, Agita, Jia, Jidong, Jonasson, Jon G, Kåberg, Martin, Kaita, Kelly D E, Kaliaskarova, Kulpash S, Kao, Jia-Horng, Kasymov, Omor T, Kelly-Hanku, Angela, Khamis, Faryal, Khamis, Jawad, Khan, Aamir G, Khandu, Lekey, Khoudri, Ibtissam, Kielland, Knut B, Kim, Do Young, Kodjoh, Nicolas, Kondili, Loreta A, Krajden, Mel, Krarup, Henrik Bygum, Kristian, Pavol, Kwon, Jisoo A, Lagging, Martin, Laleman, Wim, Lao, Wai Cheung, Lavanchy, Daniel, Lázaro, Pablo, Lazarus, Jeffrey V, Lee, Alice U, Lee, Mei-Hsuan, Li, Michael K K, Liakina, Valentina, Lim, Young-Suk, Löve, Arthur, Lukšić, Boris, Machekera, Shepherd Mufudzi, Malu, Abraham O, Marinho, Rui T, Maticic, Mojca, Mekonnen, Hailemichael D, Mendes-Correa, Maria Cássia, Mendez-Sanchez, Nahum, Merat, Shahin, Meshesha, Berhane Redae, Midgard, Håvard, Mills, Mike, Mohamed, Rosmawati, Mooneyhan, Ellen, Moreno, Christophe, Muljono, David H, Müllhaupt, Beat, Musabaev, Erkin, Muyldermans, Gaëtan, Nartey, Yvonne Ayerki, Naveira, Marcelo C M, Negro, Francesco, Nersesov, Alexander V, Njouom, Richard, Ntagirabiri, Rénovat, Nurmatov, Zuridin S, Obekpa, Solomon A, Oguche, Stephen, Olafsson, Sigurdur, Ong, Janus P, Opare-Sem, Ohene K, Orrego, Mauricio, Øvrehus, Anne L, Pan, Calvin Q, Papatheodoridis, George V, Peck-Radosavljevic, Markus, Pessoa, Mário G, Phillips, Richard O, Pimenov, Nikolay, Plaseska-Karanfilska, Dijana, Prabdial-Sing, Nishi N, Puri, Pankaj, Qureshi, Huma, Rahman, Aninda, Ramji, Alnoor, Razavi-Shearer, Devin M, Razavi-Shearer, Kathryn, Ridruejo, Ezequiel, Ríos-Hincapié, Cielo Y, Rizvi, S M Shahriar, Robaeys, Geert K M M, Roberts, Lewis R, Roberts, Stuart K, Ryder, Stephen D, Sadirova, Shakhlo, Saeed, Umar, Safadi, Rifaat, Sagalova, Olga, Said, Sanaa S, Salupere, Riina, Sanai, Faisal M, Sanchez-Avila, Juan F, Saraswat, Vivek A, Sarrazin, Christoph, Sarybayeva, Gulya, Seguin-Devaux, Carole, Sharara, Ala I, Sheikh, Mahdi, Shewaye, Abate B, Sievert, William, Simojoki, Kaarlo, Simonova, Marieta Y, Sonderup, Mark W, Spearman, C Wendy, Sperl, Jan, Stauber, Rudolf E, Stedman, Catherine A M, Su, Tung-Hung, Suleiman, Anita, Sypsa, Vana, Tamayo Antabak, Natalia, Tan, Soek-Siam, Tergast, Tammo L, Thurairajah, Prem H, Tolmane, Ieva, Tomasiewicz, Krzysztof, Tsereteli, Maia, Uzochukwu, Benjamin S C, Van De Vijver, David A M C, Van Santen, Daniela K, Van Vlierberghe, Hans, Van Welzen, Berend, Vanwolleghem, Thomas, Vélez-Möller, Patricia, Villamil, Federico, Vince, Adriana, Waheed, Yasir, Weis, Nina, Wong, Vincent W-S, Yaghi, Cesar G, Yesmembetov, Kakharman, Yosry, Ayman, Yuen, Man-Fung, Yunihastuti, Evy, Zeuzem, Stefan, Zuckerman, Eli, and Razavi, Homie A

Published
2022
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28. A nationwide cross-sectional review of in-hospital hepatitis B virus testing and disease burden estimation in Ghana, 2016 - 2021

Author

Nartey, Yvonne Ayerki, Okine, Rafiq, Seake-Kwawu, Atsu, Ghartey, Georgia, Asamoah, Yaw Karikari, Senya, Kafui, Duah, Amoako, Owusu-Ofori, Alex, Amugsi, James, Suglo, Damasus, Bampoh, Sally Afua, Hiebert, Lindsey, Njuguna, Henry, Ward, John W., Plymoth, Amelie, Roberts, Lewis Rowland, Bockarie, Ansumana Sandy, Awuku, Yaw Asante, and Obiri-Yeboah, Dorcas

Published
2022
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30. Incidence and Long-Term Outcomes of Biliary Tract Cancers in Olmsted County, Minnesota from 1976 to 2018.

Author

Nwankwo Jr., Eugene C., Guta, Amerti, Cao, Scarlett S., Yang, Ju Dong, Abdalla, Abubaker, Taha, Wesam, Larson, Joseph J., Yin, Jun, Gores, Gregory J., Cleary, Sean P., and Roberts, Lewis R.

Subjects
BILE duct tumors, POISSON distribution, GALLBLADDER tumors, SURVIVAL rate, RESEARCH funding, SEX distribution, CHOLANGIOCARCINOMA, RETROSPECTIVE studies, AGE distribution
Abstract

Simple Summary: Biliary tract cancers, which include cholangiocarcinoma, gallbladder, and ampulla of Vater cancers, are a significant health concern due to their increasing incidence and poor survival rates. Using data from the Rochester Epidemiology Project, this study tracks changes in incidence and survival rates among residents aged 20 and over in Olmsted County, Minnesota from 1976 to 2018. The findings illustrate a rise in overall biliary tract cancers from 6.53 cases to 10.25 cases per 100,000 person-years between 1976 and 2018 (p = 0.004). The incidence of intrahepatic cholangiocarcinoma has significantly increased from 0.25 to 3.93 per 100,000 person-years over the four decades, with a more pronounced increase observed in males, while gallbladder cancer incidence has decreased among women. Despite improvements in median survival times from 4.2 months to 10.8 months over the four decades (p = 0.019), the overall prognosis remains very poor. This study highlights the evolving epidemiology of these cancers and the critical need for enhanced diagnostic and treatment strategies to improve patient outcomes. Biliary tract cancers, including cholangiocarcinoma, gallbladder, and ampulla of Vater cancers, rank second among hepatobiliary cancers, known for their poor prognoses. The United States has witnessed a notable increase in intrahepatic cholangiocarcinoma incidence. This study examines the incidence and survival outcomes of biliary tract cancers in Olmsted County, Minnesota from 1976 to 2018. Using data from the Rochester Epidemiology Project (REP), residents aged 20 and above were analyzed across four eras. Incidence rates were calculated and adjusted for age and sex, and temporal trends were assessed using Poisson regression. Intrahepatic cholangiocarcinoma exhibited a significant escalation in incidence rates over time, while gallbladder cancers showed a decline among women. Median survival times for biliary tract cancers notably improved. These findings confirm the rising incidence of intrahepatic cholangiocarcinoma and suggest improving survival rates. Nevertheless, the overall prognosis for biliary tract cancers remains very poor, emphasizing the continual need for enhanced management strategies and further research. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Direct Imaging in Reflected Light: Characterization of Older, Temperate Exoplanets With 30-m Telescopes

Author

Artigau, Etienne, Bernstein, Rebecca A, Brandt, Timothy, Chilcote, Jeffrey, Close, Laird, Crossfield, Ian, Delorme, Jacques-Robert, Dressing, Courtney, Fitzgerald, Michael P, Fortney, Jonathan, Howard, Andrew, Frazin, Richard, Jovanovic, Nemanja, Konopacky, Quinn, Lozi, Julien, Males, Jared R, Marois, Christian, Mazin, Benjamin A, Millar-Blanchaer, Max A, Morzinski, Katie M, Roberts, Lewis, Serabyn, Eugene, Vasisht, Gautam, Wallace, J Kent, and Wang, Ji

Subjects
astro-ph.IM
Abstract

Direct detection, also known as direct imaging, is a method for discoveringand characterizing the atmospheres of planets at intermediate and wideseparations. It is the only means of obtaining spectra of non-transitingexoplanets. Characterizing the atmospheres of planets in the

Published
2018

32. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases

Author

Marrero, Jorge A, Kulik, Laura M, Sirlin, Claude B, Zhu, Andrew X, Finn, Richard S, Abecassis, Michael M, Roberts, Lewis R, and Heimbach, Julie K

Subjects
Good Health and Well Being, Antineoplastic Agents, Carcinoma, Hepatocellular, Early Detection of Cancer, Female, Hepatectomy, Humans, Liver, Liver Neoplasms, Liver Transplantation, Male, Neoplasm Staging, United States, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Published
2018

33. Imaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta‐analysis

Author

Roberts, Lewis R, Sirlin, Claude B, Zaiem, Feras, Almasri, Jehad, Prokop, Larry J, Heimbach, Julie K, Murad, M Hassan, and Mohammed, Khaled

Subjects
Cancer, Liver Cancer, Clinical Research, Liver Disease, Chronic Liver Disease and Cirrhosis, Clinical Trials and Supportive Activities, Rare Diseases, Digestive Diseases, Biomedical Imaging, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Adult, Carcinoma, Hepatocellular, Contrast Media, Female, Humans, Image Interpretation, Computer-Assisted, Liver Neoplasms, Magnetic Resonance Imaging, Male, Middle Aged, Multimodal Imaging, Reproducibility of Results, Tomography, X-Ray Computed, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Abstract

Multiphasic computed tomography (CT) and magnetic resonance imaging (MRI) are both used for noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. To determine if there is a relative diagnostic benefit of one over the other, we synthesized evidence regarding the relative performance of CT, extracellular contrast-enhanced MRI, and gadoxetate-enhanced MRI for diagnosis of HCC in patients with cirrhosis. We also assessed whether liver biopsy versus follow-up with the same versus alternative imaging is best for CT-indeterminate or MRI-indeterminate liver nodules in patients with cirrhosis. We searched multiple databases from inception to April 27, 2016, for studies comparing CT with extracellular contrast-enhanced MRI or gadoxetate-enhanced MRI in adults with cirrhosis and suspected HCC. Two reviewers independently selected studies and extracted data. Of 33 included studies, 19 were comprehensive, while 14 reported sensitivity only. For all tumor sizes, the 19 comprehensive comparisons showed significantly higher sensitivity (0.82 versus 0.66) and lower negative likelihood ratio (0.20 versus 0.37) for MRI over CT. The specificities of MRI versus CT (0.91 versus 0.92) and the positive likelihood ratios (8.8 versus 8.1) were not different. All three modalities performed better for HCCs ≥2 cm. Performance was poor for HCCs

Published
2018

34. Molecular testing for the clinical diagnosis of fibrolamellar carcinoma

Author

Graham, Rondell P, Yeh, Matthew M, Lam-Himlin, Dora, Roberts, Lewis R, Terracciano, Luigi, Cruise, Michael W, Greipp, Patricia T, Zreik, Riyam T, Jain, Dhanpat, Zaid, Nida, Salaria, Safia N, Jin, Long, Wang, Xiaoke, Rustin, Jeanette G, Kerr, Sarah E, Sukov, William R, Solomon, David A, Kakar, Sanjay, Waterhouse, Emily, Gill, Ryan M, Ferrell, Linda, Alves, Venancio AF, Nart, Deniz, Yilmaz, Funda, Roessler, Stephanie, Longerich, Thomas, Schirmacher, Peter, and Torbenson, Michael S

Subjects
Biotechnology, Cancer, Genetics, Adult, Biomarkers, Tumor, Carcinoma, Hepatocellular, Cyclic AMP-Dependent Protein Kinase Catalytic Subunits, Female, HSP40 Heat-Shock Proteins, Humans, In Situ Hybridization, Fluorescence, Male, Oncogene Proteins, Fusion, Retrospective Studies, Young Adult, Medical and Health Sciences, Pathology
Abstract

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone.

Published
2018

35. AASLD guidelines for the treatment of hepatocellular carcinoma

Author

Heimbach, Julie K, Kulik, Laura M, Finn, Richard S, Sirlin, Claude B, Abecassis, Michael M, Roberts, Lewis R, Zhu, Andrew X, Murad, M Hassan, and Marrero, Jorge A

Subjects
Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Published
2018

42. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.

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, Cancer Genome Atlas Network, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, and Kwong, Lawrence N

Subjects
Cancer Genome Atlas Network, Liver, Chromatin, Mitochondria, Humans, Cholangiocarcinoma, Bile Duct Neoplasms, Liver Neoplasms, Pancreatic Neoplasms, Isocitrate Dehydrogenase, Nuclear Proteins, Transcription Factors, RNA, Messenger, Genomics, DNA Methylation, Gene Expression Regulation, Neoplastic, Mutation, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Promoter Regions, Genetic, RNA, Long Noncoding, ARID1A, DNA methylation, IDH, RNA sequencing, TCGA, cholangiocarcinoma, integrative genomics, lncRNAs, multi-omics, whole exome, RNA, Messenger, Gene Expression Regulation, Neoplastic, and over, Promoter Regions, Genetic, Long Noncoding, Biochemistry and Cell Biology, Medical Physiology
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

43. p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic Stellate Cell Activity, Fibrosis, and Liver Cancer

Author

Duran, Angeles, Hernandez, Eloy D, Reina-Campos, Miguel, Castilla, Elias A, Subramaniam, Shankar, Raghunandan, Sindhu, Roberts, Lewis R, Kisseleva, Tatiana, Karin, Michael, Diaz-Meco, Maria T, and Moscat, Jorge

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Nutrition, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Liver Cancer, Rare Diseases, Liver Disease, Cancer, Oral and gastrointestinal, Animals, HEK293 Cells, Hepatic Stellate Cells, Humans, Liver Cirrhosis, Liver Neoplasms, Mice, Mice, Knockout, Receptors, Calcitriol, Retinoid X Receptors, Sequestosome-1 Protein, Signal Transduction, fibrosis, hepatic stellate cells, hepatocellular carcinoma, inflammation, liver cancer, non-alcoholic steatohepatitis, nuclear receptors, p62, sequestosome-1, vitamin D receptor, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Hepatic stellate cells (HSCs) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSCs inhibits liver inflammation and fibrosis. We found that p62/SQSTM1, a protein upregulated in liver parenchymal cells but downregulated in HCC-associated HSCs, negatively controls HSC activation. Total body or HSC-specific p62 ablation potentiates HSCs and enhances inflammation, fibrosis, and HCC progression. p62 directly interacts with VDR and RXR promoting their heterodimerization, which is critical for VDR:RXR target gene recruitment. Loss of p62 in HSCs impairs the repression of fibrosis and inflammation by VDR agonists. This demonstrates that p62 is a negative regulator of liver inflammation and fibrosis through its ability to promote VDR signaling in HSCs, whose activation supports HCC.

Published
2016

44. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

Author

Roberts, Lewis R, Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibbs, Richard, Roszik, Jason, Covington, Kyle, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva M, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Stuart, Josh, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Laird, Peter W, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael, Kleiner, David E, Wheeler, David A, Mcree, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, and Kwong, Lawrence N

Subjects
Gastroenterology & Hepatology, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology
Published
2016

46. Augustine and Enjambment: A source for Hopkins's term 'rove over'.

Author

Roberts, Lewis

Subjects
*COMPLEXITY (Philosophy), *SPEECH, *NEGOTIATION, *AESTHETICS of art, *MUSIC theory
Abstract

This essay examines the origins of Gerard Manley Hopkins's term "rove over" in relation to enjambment in his poetry. Hopkins's approach to prosody is not systematic and encompasses various works and casual thoughts. The term "rove over" refers to the ambiguity of reading across line breaks and may have been influenced by St. Augustine's treatise on poetics, De Musica. Augustine's synthesis of rhetoric and theology in De Musica aligns with Hopkins's hybrid thinking, and there are similarities between passages in the treatise and Hopkins's writing. The article explores the connection between the terms "rove over" and "provolutio" in the works of Gerard Manley Hopkins and Augustine, both of which describe the ambivalent function of enjambment in poetry. The author suggests that Hopkins may have derived his term from Augustine's "provolutio," as both terms share structural, semantic, and phonetic similarities. The article also discusses the influence of Augustine's theological and philosophical thinking on Hopkins's work, particularly in relation to the acceptance of contradiction. The author concludes that the terms "rove over" and "provolutio" are not merely technical terms, but are linked to broader philosophical and theological concepts. [Extracted from the article]

Published
2024
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48. Children with Chronic Hepatitis B in the United States and Canada

Author

Schwarz, Kathleen B, Cloonan, Yona Keich, Ling, Simon C, Murray, Karen F, Rodriguez-Baez, Norberto, Schwarzenberg, Sarah Jane, Teckman, Jeffrey, Ganova-Raeva, Lilia, Rosenthal, Philip, Schwarz, Kathleen, Murray, Karen, Belle, Steven, Janssen, Harry, Ling, Simon, Terrault, Norah, Roberts, Lewis R, Di Bisceglie, Adrian, Teckman, Jeffery, Ganova-Raeva, Lilia Milkova, Li, Hongxia, Mogul, Douglas, Anders, Robert, Kafka, Kim, Riggs, Shannon M, Nagy, Rosemary, Cerkoski, Jacki, Yuan, Caitlin, Swan, Rosemary, O'Connor, Constance, Rodgers-Augustyniak, Laurie A, Montanye, Shirley, Fleck, Shannon, Langlois, Camille, Cooper, Kara L, Danielson, Michelle, Haller, Tamara, Johnson, Geoffrey, Kelley, Stephanie, Lawlor, Sharon, Li, Ruosha, Lombardero, Manuel, MacGregor, Joan M, Pelesko, Andrew, Stoliker, Donna, Walters, Barbara, and Zadorozny, Ella

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis - B, Hepatitis, Liver Disease, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Genetics, Infectious Diseases, 2.1 Biological and endogenous factors, Good Health and Well Being, Adolescent, Canada, Child, Child, Preschool, Cross-Sectional Studies, Female, Genotype, Hepatitis B virus, Hepatitis B, Chronic, Humans, Infant, Male, United States, Hepatitis B Research Network, Human Movement and Sports Sciences, Paediatrics and Reproductive Medicine, Pediatrics, Paediatrics
Abstract

ObjectivesTo test the hypothesis that children with chronic hepatitis B living in the US and Canada would have international origins and characteristic hepatitis B virus (HBV) genotypes and laboratory profiles.Study designClinical characteristics of children enrolled in the Hepatitis B Research Network were collected from 7 US and Canadian centers.ResultsChildren (n = 343) with an age range of 1.0-17.8 years were enrolled; 78% of the children were Asian, 55% were adopted, and 97% had international origins with either the child or a parent born in 1 of 31 countries. The majority had HBV genotype B (43%) or C (32%), and the remainder had genotype A (5%), D (16%), E (4%), or multiple (

Published
2015

49. Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy

Author

Kottke, Timothy, Tonne, Jason, Evgin, Laura, Driscoll, Christopher B., van Vloten, Jacob, Jennings, Victoria A., Huff, Amanda L., Zell, Brady, Thompson, Jill M., Wongthida, Phonphimon, Pulido, Jose, Schuelke, Matthew R., Samson, Adel, Selby, Peter, Ilett, Elizabeth, McNiven, Mark, Roberts, Lewis R., Borad, Mitesh J., Pandha, Hardev, Harrington, Kevin, Melcher, Alan, and Vile, Richard G.

Published
2021
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50. Role of Killer cell immunoglobulin-like receptors (KIR) genes in stages of HIV-1 infection among patients from Burkina Faso

Author

Sorgho Pegdwendé Abel, Djigma Florencia Wendkuuni, Martinson Jeremy James, Yonli Albert Théophane, Nagalo Bolni Marius, Compaore Tégwindé Rebeca, Diarra Birama, Sombie Herman Karim, Simpore Abibou, Zongo Arsène Wendpagnangdé, Ouattara Abdoul Karim, Soubeiga Serge Théophile R., Traore Lassina, Yelemkoure Edwige T, Kiendrebeogo Isabelle Touwendpoulimdé, Roberts Lewis R., and Simpore Jacques

Subjects
kir gene, hiv-1, t cd4, viral load, burkina faso, Biology (General), QH301-705.5
Abstract

A cluster of specialized KIR genes of specialized KIR genes has been shown to be associated with susceptibility or resistance to viral infections in humans. Therefore, this pilot study, this pilot investigation sought to determine the frequencies of KIR genes human immunodeficiency virus type 1( HIV-1) patients and establish their potential clinical involvement in disease progression and staging.

Published
2019
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