Karavias, Dimitrios D.
Mayo Clinic
for the Adeno-IPMN2 Collaborative
Citations 2
Contemporary Adjuvant Chemotherapy for Intraductal Papillary Mucinous Neoplasms
Haugk, Beate , White, Steven, Marchegiani, Giovanni, Holmberg, Marcus, Zerbi, Alessandro, Lu, Zipeng , Inoue, Y., Choi, Munseok , Kang, Chang Moo, Visser, B., Corpelijn, Lieke, Andersson, Bodil, Bereza-Carlson, Paulina, Björnsson, Bergthor, Wennerblom, Johanna, Goh, Brian K. P., Hartman, V., Ahmad, Syed, Patel, Sameer, Berrevoet, Frederik, Mortensen, Kim Erlend, Roberts, K., Lynch, Calum, Gupta, Amit, Kleeff, Joerg, Addeo, Pietro, Friess, Helmut, Koea, Jonathan, Gomez, Dhanny , Gordon-Weeks, Alex, Doria, Cataldo, Tzimas, Georgios, Franklin, O., Månsson, C., Cabús, Santiago Sánchez, Bhogal, Ricky H. , Pathak, Samir, Honselmann, Kim Christin, Balakrishnan, Anita, Mann, Kulbir , Gill, Anthony J., Mittal, A, Samra, Jas, Athwal, Tejinderjit, Loveday, Benjamin, Bhardwaj, Neil, Menon, Krishna, Thapa, Prabin, Matsumoto, Ippei, Jamieson, Nigel, Rebours, Vinciane, Descourvières, Clémence, Davidson, BR, Soreide, Kjetil, Pandanaboyana, Sanjay, Collaborative, Adeno-IPMN2, Kumar, Ajit, González, Carol Natalia Clavijo, Lam, Shi, L’Official-German, Ivan, Bergner, Tina, Rosso, Edoardo , Giulianotti, Pier Cristoforo , Morreau, Mathew , Dili, Alexandra, Sotiropoulou, Maria , Kuzman, Matta , Büyükkasap, Ahmet Çağrı, Uludağ, Gökhan, McGuigan, Mari-Claire , Chouari, Tarak , Dogul, Ahmet, Doğu, Doğukan , Rebelo, Artur, Holewik, Franziska Bernadette, Plesa-Furda, Roxana, Revoredo, Fernando, Galanis, Ilias , Maharjan, Dhiresh, Ghorbani, Poya , Lind, Max, Ami, Katsuya , Vijayashanker, Aarathi , Alsaoudi, Tareq , Lundgren, Linda , Ellisa, Katrina, Hong, Paul , Gupta, Archit, MartinXu, Congde, Konstantoudakis, Georgios, Christophides, Thalis, Spurring, Eleanor Margaret, Iwao, Yasuhito, Pirklc, Martin, Vaitha, Ruhi , Tiwari, Navneet, Sheel, Andrea, Kotecha, Krishna , Stavrou, Gregor A., Patel, Rikhilroy, Misca, Mihaela , Hammond, John, Roalso, Marcus Thomas Thor, Soomro, Faiza H, Halimi, Asif , Kendall, Timothy, Patel, Visad, Stankic, Dunja, Dries, Pieter , Hein, Charlotte, Betram, Julia, Jacob, Rosetta, Wilson, Gregory, Redas, Souheil, Poškus, Augustas, Mosert, Paula Lucia, Šilinskaitė, Ugnė , Hirose, Yuki, Liu, Xue, Standaert, Lars, Kay, Tegan J, Nishida, Kenji, Peddakota, Vivek , Gupta, Amit , Kang, Chang Moo , Ven Fong, Zhi, Kang, Chang Moo , Lucocq, James E. , Marchegiani, Giovanni , Zerbi, Alessandro , Pagnanelli, Michele , Visser, B. , Andersson, Bodil , Bereza‐Carlson, Paulina , Björnsson, Bergþór , Wennerblom, Johanna Hansson , Labori, Knut Jørgen , Goh, Brian K P , Hartman, Vera , Berrevoet, Frederik Christiaan , Ausania, Fabio , Bertrand, Claude , Kleeff, Joerg, Addeo, Pietro , Bellotti, Ruben , Fong, Zhi Ven , Friess, Helmut , Koea, Jonathan , Gordon-Weeks, Alex Nicolas , Doria, Cataldo , Franklin, Oskar , Pathak, Samir , Honselmann, Kim C. , Balakrishnan, Anita , Harrison, Ewen M. , Gill, A J, Mittal, Anubhav, Samra, Jas , Athwal, Tejinderjit , Loveday, Benjamin P. T. , Teh, Catherine , Bhardwaj, Neil , Menon, Krishna, Matsumoto, Ippei , Jamieson, Nigel , Rebours, Vinciane , Søreide, Kjetil , Martlı, Hüseyin Fahri , Roeyen, Geert , Antonakis, Pantelis T. , Bramis, Konstantinos , Hall, Lewis A , Valle, Valentina , Connor, Saxon J. , Kapiris, Stylianos A. , Kerem, Mustafa , Rebelo, Artur , Plesa-Furda, R., Filho, Omero Pereira da Costa , Galanis, Ilias, Konstantoudakis, Georgios, Christophides, Thalis, McGuinness, Matthew James , Yaqub, Sheraz , Pellegrini, Riccardo , Perri, Giampaolo , Sheel, Andrea , Sheen, Amy , Evans, Daisy, Ghamarnejad, Omid , Karavias, Dimitrios D. , Roalsø, Marcus T. T. , Stankic, Dunja , Grubor, Nikica , Gulla, Aistė , Furukawa, Takaaki , Hirose, Yuki , Yin, Lingdi
JAMA Network Open | March 27, 2026 | Volume: 9 | Issue: 3 | Pages: e263688
10.1001/jamanetworkopen.2026.3688
Importance Adjuvant chemotherapy regimens may be administered after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMNs), although the evidence supporting their use is limited. Objective To evaluate the survival benefit associated with contemporary adjuvant chemotherapy regimens after resection in A-IPMNs between 2017 and 2023. Design, Setting, and Participants This retrospective cohort study was an international, multicenter study with 69 participating centers across Europe, North America, South America, and the Asia-Pacific region. Patients undergoing resection for A-IPMNs were included. Data were analyzed from May to August 2025. Intervention Contemporary adjuvant chemotherapy regimens, such as gemcitabine-capecitabine (GemCap); 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX), modified FOLFIRINOX (mFOLFIRINOX), and S-1. Main Outcome and Measure Overall survival (months). Results Among 1321 patients (median [IQR] age 70 [63 to 76] years; 713 males [54.0%] and 608 females [46.0%]), 781 patients (59.1%) received adjuvant chemotherapy, while in 181 patients (13.7%) it was omitted due to poor patient fitness. Of patients who received adjuvant chemotherapy, 568 patients (72.6%) received contemporary regimens, including GemCap (232 patients [29.7%]), FOLFIRINOX (176 patients [22.5%]), mFOLFIRINOX (71 patients [9.1%]), and S-1 (70 patients [9.0%]). The median (IQR) follow-up for the cohort was 64.2 (40.4 to 85.0) months, and the median overall survival was 73.8 months (95% CI, 66.4 to 81.9 months). After 90-day landmark analysis and exclusion of patients ineligible for chemotherapy, adjuvant chemotherapy vs no adjuvant chemotherapy (propensity score–matched populations, 243:243 patients) was not associated with improved overall survival (median, 82.3 months; 95% CI, 78.2 months to not applicable [NA] vs not reached; 95% CI, 75.3 months to NA; P = .58). Contemporary regimens vs no adjuvant chemotherapy (propensity score–matched populations, 309:309 patients) was not associated with longer survival, and a mean survival benefit greater than 4.2 months over 5 years was excluded (difference in restricted mean survival, 1.26 months; 95%, −1.72 to 4.24 months). Treatment outcomes did not vary by chemotherapy regimen or disease characteristic (eg, N stage or carbohydrate antigen 19-9 level). Conclusions and Relevance In this study, contemporary adjuvant chemotherapy was not associated with improved overall survival in A-IPMNs, and a randomized clinical trial is indicated.
Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming
Κουτσιούμπα, Μαρίνα, Hatziapostolou, Maria , Polytarchou, Christos , Tolosa, Ezequiel J. , Almada, Luciana L. , Mahurkar‐Joshi, Swapna , Williams, Jennifer L., Tirado-Rodriguez, Ana B., Huerta‐Yépez, Sara , Kourea, Helen P., Poultsides, George A. , Dawson, David W. , Donahue, Timothy R. , Fernández-Zapico, Martín E. , Iliopoulos, Dimitrios , Karavias, Dimitrios D. , Struhl, Kevin
Gut | October 19, 2018 | Volume: 68 | Issue: 7 | Pages: 1271-1286
Objective Despite advances in the identification of epigenetic alterations in pancreatic cancer, their biological roles in the pathobiology of this dismal neoplasm remain elusive. Here, we aimed to characterise the functional significance of histone lysine methyltransferases (KMTs) and demethylases (KDMs) in pancreatic tumourigenesis. Design DNA methylation sequencing and gene expression microarrays were employed to investigate CpG methylation and expression patterns of KMTs and KDMs in pancreatic cancer tissues versus normal tissues. Gene expression was assessed in five cohorts of patients by reverse transcription quantitative-PCR. Molecular analysis and functional assays were conducted in genetically modified cell lines. Cellular metabolic rates were measured using an XF24-3 Analyzer, while quantitative evaluation of lipids was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Subcutaneous xenograft mouse models were used to evaluate pancreatic tumour growth in vivo. Results We define a new antitumorous function of the histone lysine (K)-specific methyltransferase 2D (KMT2D) in pancreatic cancer. KMT2D is transcriptionally repressed in human pancreatic tumours through DNA methylation. Clinically, lower levels of this methyltransferase associate with poor prognosis and significant weight alterations. RNAi-based genetic inactivation of KMT2D promotes tumour growth and results in loss of H3K4me3 mark. In addition, KMT2D inhibition increases aerobic glycolysis and alters the lipidomic profiles of pancreatic cancer cells. Further analysis of this phenomenon identified the glucose transporter SLC2A3 as a mediator of KMT2D-induced changes in cellular, metabolic and proliferative rates. Conclusion Together our findings define a new tumour suppressor function of KMT2D through the regulation of glucose/fatty acid metabolism in pancreatic cancer.