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The spatial zonation of the murine placental vasculature is specified by epigenetic mechanisms

Developmental Cell 2025年第10期60卷 1467-1482.e8页

作者： Gehrs, Stephanie Jakab, Moritz Gutjahr, Ewgenija Gu, Zuguang Weichenhan, Dieter Mallm, Jan-Philipp Mogler, Carolin Schlesner, Matthias Plass, Christoph Schlereth, Katharina Augustin, Hellmut G. Division of Vascular Oncology and Metastasis German Cancer Research Center (DKFZ) Heidelberg 69120 Germany European Center for Angioscience (ECAS) Medical Faculty Mannheim Heidelberg University Mannheim 68167 Germany Faculty of Biosciences Heidelberg University Heidelberg 69120 Germany Institute of Pathology University Clinic Heidelberg Heidelberg 69120 Germany Computational Oncology Group Molecular Precision Oncology Program National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg 69120 Germany Division of Cancer Epigenomics German Cancer Research Center (DKFZ) Heidelberg 69120 Germany Division of Chromatin Networks German Cancer Research Center (DKFZ) and Bioquant Heidelberg 69120 Germany Institute of Pathology TUM School of Medicine Technical University of Munich Munich 80333 Germany Biomedical Informatics Data Mining and Data Analytics Faculty of Applied Computer Science and Medical Faculty University of Augsburg Augsburg 86159 Germany

The labyrinthian fetoplacental capillary network is vital for proper nourishment of the developing embryo. Dysfunction of the maternal-fetal circulation is a primary cause of placental insufficiency. Here, we show that the spatial zonation of the murine placental labyrinth vasculature is controlled by flow-regulated epigenetic mechanisms. Spatiotemporal transcriptomic profiling identified a gradual change in the expression of epigenetic enzymes, including the de novo DNA methyltransferase 3a (DNMT3A). Loss of Dnmt3a resulted in DNA hypomethylation and perturbation of zonated placental gene expression. The resulting global DNA hypomethylation impaired the angiogenic capacity of endothelial cells. Global or endothelium-predominant deletion of Dnmt3a resulted in impaired placental vascularization and fetal growth retardation (FGR). Human placental endothelial gene expression profiling associated preeclampsia with reduced DNMT3A expression. Collectively, our study identified DMNT3A as critical methylome-regulator of placental endothelial gene expression and function with clinical implications for placental dysfunction, as it occurs during preeclampsia or FGR. © 2024 The Authors

关键词： angiogenesis DNA methylation DNMT3A epigenetic regulation growth retardation placental endothelium spatial zonation

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The exposome and pancreatic cancer, lifestyle and environmental risk factors for PDAC

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Seminars in Cancer Biology 2025年 113卷 100-129页

作者： Peduzzi, Giulia Archibugi, Livia Farinella, Riccardo de Leon Pisani, Ruggero Ponz Vodickova, Ludmila Vodicka, Pavel Kraja, Bledar Sainz, Juan Bars-Cortina, David Daniel, Neil Silvestri, Roberto Uysal-Onganer, Pinar Landi, Stefano Dulińska-Litewka, Joanna Comandatore, Annalisa Campa, Daniele Hughes, David J. Rizzato, Cosmeri Department of Biology University of Pisa Pisa Italy Pancreato-Biliary Endoscopy and Endosonography Division Pancreas Translational and Clinical Research Center IRCCS Ospedale San Raffaele Milan Italy Biomedical Center Martin Bioinformatic Center Comenius University in Bratislava Jessenius Faculty of Medicine in Martin Slovakia Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic University Clinic of Gastrohepatology University Hospital Center Mother Teresa Tirana Albania Department of Biochemistry and Molecular Biology University of Granada Granada Spain Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) Madrid 28029 Spain GENYO. Centre for Genomics and Oncological Research. Genomic Oncology department Granada Spain Instituto de Investigación Biosanitaria Ibs.Granada Granada Spain Institut Català d’Oncologia (ICO) IDIBELL Unit of Biomarkers and Susceptibility (UBS) Oncology Data Analytics Program (ODAP) Catalan Institute of Oncology (ICO) L′Hospitalet del Llobregat Barcelona Spain Institut Català d’Oncologia (ICO) IDIBELL ONCOBELL Program Bellvitge Biomedical Research Institute (IDIBELL) L′Hospitalet de Llobregat Barcelona Spain Molecular Epidemiology of Cancer Group UCD Conway Institute School of Biomolecular and Biomedical Science University College Dublin Dublin Ireland Cancer Mechanisms and Biomarkers Research Group School of Life Sciences University of Westminster London UK Chair of Medical Biochemistry Medical College Jagiellonian University Krakow Poland General Surgery Unit Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Italy

AbstractPancreatic cancer (PC), particularly pancreatic ductal adenocarcinoma (PDAC), is a significant global health issue with high mortality rates. PDAC, though only 3 % of cancer diagnoses, causes 7 % of cancer deaths due to its severity and asymptomatic early stages. Risk factors include lifestyle choices, environmental exposures, and genetic predispositions. Conditions like new-onset type 2 diabetes and chronic pancreatitis also contribute significantly. Modifiable risk factors include smoking, alcohol consumption, non-alcoholic fatty pancreatic disease (NAFPD), and obesity. Smoking and heavy alcohol consumption increase PC risk, while NAFPD and obesity, particularly central adiposity, contribute through chronic inflammation and insulin resistance. Refined sugar and sugar-sweetened beverages (SSBs) are also linked to increased PC risk, especially among younger individuals. Hormonal treatments and medications like statins, aspirin, and metformin have mixed results on PC risk, with some showing protective effects. The gut microbiome influences PC through the gut-pancreas axis, with disruptions leading to inflammation and carcinogenesis. Exposure to toxic substances, including heavy metals and chemicals, is associated with increased PC risk. Glycome changes, such as abnormal glycosylation patterns, are significant in PDAC development and offer potential for early diagnosis. Interactions between environmental and genetic factors are crucial in PDAC susceptibility. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) linked to PDAC, but gene-environment interactions remain largely unexplored. Future research should focus on polygenic risk scores (PRS) and large-scale studies to better understand these interactions and their impact on PDAC risk.

关键词： Exposome Pancreatic Cancer Risk factors

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Capecitabine treatment patterns in patients with gastroesophageal cancer in the United States

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World Journal of Gastroenterology 2009年第35期15卷 4415-4422页

作者： Muhammad Wasif Saif Nianwen Shi Susan Zelt Gastrointestinal Cancers Program Yale Medical OncologyNew HavenCT 06519United States Thomson Reuters CambridgeMA 02140 United States Medical Data Management and Analytics Roche NutleyNJ 07110United States

AIM： To assess the use of capecitabine-based therapy and associated complication rates in patients with gastroesophageal cancer （GEC） in a real-world treat- ment setting. METHODS： Patients with claims between 2004 and 2005 were identified from the Thomson Reuters MarketScan databases. Capecitabine regimens were compared with 5-fluorouracU （5-FU） and other chemotherapy regimens, and were stratified by treatment setting. RESULTS： We identified 1013 patients with GEC： approximately half had treatment initiated with a 5-FU regimen, whereas 11% had therapy initiated with a capecitabine regimen. The mean capecitabine dose overall was 2382 ± 1118 mg/d, and capecitabine was used as monotherapy more often than in combination. Overall, 5-FU regimens were the most common treat- ment option in neoadjuvant and adjuvant settings, while other non-capecitabine regimens were used more widely in first- and second-line settings. The overall unadjusted complication rate for capecitabine regimens was about half of that seen with 5-FU regimens. In multivariate analyses, capecitabine recipients had a 51% （95% CI： 26%-81%） lower risk of developing any complication than 5-FU recipients did. The risk of developing bone marrow, constitutional, gastrointestinal tract, infectious, or skin complications was lower with capecitabine therapy than with ***： Capecitabine appeared to have a favorable side effect profile compared with 5-FU, which indicates that it may be a treatment option for GEC.

关键词： Capecitabine 5-fluorouracil Hand-footsyndrome Gastroesophageal cancer

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Identification and external validation of tumor DNA methylation panel for the recurrence risk stratification of stage II colon cancer

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Translational oncology 2025年 57卷 102405-102405页

作者： Yuan, Tanwei Edelmann, Dominic Moreno, Víctor Georgii, Elisabeth de Andrade e Sousa, Lisa Barros Pelin, Helena Jiang, Xiaofeng Kather, Jakob Nikolas Tagscherer, Katrin E. Roth, Wilfried Bewerunge-Hudler, Melanie Brobeil, Alexander Kloor, Matthias Bläker, Hendrik Brenner, Hermann Hoffmeister, Michael Division of Clinical Epidemiology and Aging Research German Cancer Research Center (DKFZ) Heidelberg Germany Medical Faculty Heidelberg Heidelberg University Heidelberg Germany Division of Biostatistics German Cancer Research Center (DKFZ) Heidelberg Germany Oncology Data Analytics Program Catalan Institute of Oncology (ICO). Hospitalet de Llobregat Barcelona Spain Colorectal Cancer Group ONCOBELL Bellvitge Biomedical Research Institute (IDIBELL). Hospitalet de Llobregat Barcelona Spain Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP) Madrid Spain Department of Clinical Sciences Faculty of Medicine and health Sciences and Universitat de Barcelona Institute of Complex Systems (UBICS) University of Barcelona Barcelona Spain Helmholtz AI Helmholtz Munich Munich Germany Else Kroener Fresenius Center for Digital Health Technical University Dresden Dresden Germany Institute of Pathology University Medical Center Mainz Mainz Germany Institute of Pathology Heidelberg University Hospital Heidelberg Germany Microarray Core Facility German Cancer Research Center (DKFZ) Heidelberg Germany Institute of Pathology University of Leipzig Medical Center Leipzig Germany German Cancer Consortium (DKTK) German Cancer Research Center (DKFZ) Heidelberg Germany

Background: Tailoring surveillance and treatment strategies for stage II colon cancer (CC) after curative surgery remains challenging, and personalized approaches are lacking. We aimed to identify a gene methylation panel capable of stratifying high-risk stage II CC patients for recurrence beyond traditional clinical variables. Methods: Genome-wide tumor tissue DNA methylation data were analyzed from 562 stage II CC patients who underwent surgery in Germany (DACHS study). The cohort was divided into a training set (N = 395) and an internal validation set (N = 131), with external validation performed on 97 stage II CC patients from Spain. DNA methylation markers were primarily selected using the Elastic Net Cox model. The resulting prognostic index (PI), a combination of clinical factors and selected methylation markers, was compared to baseline models using clinical variables or microsatellite instability (MSI), with discrimination and prediction accuracy assessed through time-dependent receiver operating characteristic curves (AUC) and Brier scores. Results: The final PI incorporated age, sex, tumor stage, location, and 27 DNA methylation markers. The PI consistently outperformed the baseline model including age, sex, and tumor stage in time-dependent AUC across validation cohorts (e.g., 1-year AUC and 95 % confidence interval: internal validation set, PI: 0.66, baseline model: 0.52;external validation set, PI: 0.72, baseline model: 0.64). In internal validation, the PI also showed a consistently improved time-dependent AUC compared with a combination of MSI and tumor stage only. Nevertheless, the PI did not improve the prediction accuracy of CC recurrence compared to the baseline model. Conclusions: This study identified 27 tumor tissue DNA methylation biomarkers that improved the discriminative power in classifying recurrence risk among stage II colon cancer patients. While this methylation panel alone lacks sufficient prediction accuracy for clinical application

关键词： Colon cancer DNA methylation panel Prognostic index Recurrence risk

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Correction: Spatial organization of B lymphocytes and prognosis prediction in patients with gastric cancer

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Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2025年 2025 May 16页

作者： Ryan Yong Kiat Tay Manavi Sachdeva Haoran Ma Young-Woo Kim Myeong-Cherl Kook Hyunki Kim Jae-Ho Cheong Lindsay C Hewitt Katharina Nekolla Günter Schmidt Takaki Yoshikawa Takashi Oshima Tomio Arai Supriya Srivastava Ming Teh Xuewen Ong Su Ting Tay Taotao Sheng Joseph J Zhao Patrick Tan Heike I Grabsch Raghav Sundar Yong Loo Lin School of Medicine National University of Singapore 1E Kent Ridge Road Singapore 119228 Singapore. Department of Haematology-Oncology National University Cancer Institute National University Hospital Singapore Singapore. Cancer and Stem Cell Biology Program Duke-NUS Medical School Singapore Singapore. Department of Cancer Policy and Population Health National Cancer Center Graduate School of Cancer Science and Policy and Center for Gastric Cancer and Department of Surgery National Cancer Center Goyang Republic of Korea. Center for Gastric Cancer Department of Pathology National Cancer Center Goyang Republic of Korea. Department of Pathology Yonsei University College of Medicine Seoul Republic of Korea. Department of Surgery Yonsei University College of Medicine Seoul Republic of Korea. Department of Pathology GROW Research Institute for Oncology and Reproduction Maastricht University Medical Center+ Maastricht The Netherlands. Department of Precision Medicine GROW School for Oncology and Reproduction Maastricht University Center+ Maastricht The Netherlands. Computational Pathology Oncology R&D AstraZeneca Munich Germany. Department of Surgery Kanagawa Cancer Center Yokohama Japan. Department of Surgery Yokohama City University Yokohama Japan. Department of Surgery Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Tokyo Japan. Department of Pathology Tokyo Metropolitan Institute for Geriatrics and Gerontology Tokyo Japan. Department of Medicine National University of Singapore Singapore Singapore. Department of Pathology National University Hospital Singapore Singapore. Genome Institute of Singapore Agency for Science Technology and Research Singapore Singapore. Cancer Science Institute of Singapore National University of Singapore Singapore Singapore. Cellular and Molecular Research National Cancer Centre Singapore Singapore. Singhealth/Duke-NUS Institute of Precision Medicine National Heart Centre Singapore

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Using the SEER-Medicare data to Assess Incident Chronic Myeloid Leukemia and Bladder Cancer Cases Missed by Cancer Registries

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Journal of the National Cancer Institute - Monographs 2020年第55期2020卷 31-38页

作者： Lam, Clara J. K. Warren, Joan L. Nielsen, Matthew Smith, Angela Boyd, Eric Barrett, Michael J. Mariotto, Angela B. Data Analytics Branch Surveillance Research Program Division of Cancer Control and Population Sciences National Cancer Institute Rockville MD United States Healthcare Assessment Research Branch Healthcare Delivery Research Program Division of Cancer Control and Population Sciences National Cancer Institute Rockville MD United States UNC Department of Urology Oncology UNC Lineberger Cancer Center Chapel Hill NC United States Information Management Services Inc. Calverton MD United States

The growing use of oral systemic therapies and transition of some cancer treatments to the outpatient setting makes capturing all cancer case patients more difficult. We aim to develop algorithms to identify potentially missed incident case patients and estimate impact on incidence rates. We reviewed claims from SEER-Medicare 5% noncancer control patient sample to identify potentially missed chronic myeloid leukemia (CML) and bladder case patients based on diagnosis codes, cancer-related treatments, and oncology consultations. Observed rates of definite missed CML and definite and probable missed bladder case patients were calculated and the impact of missed case patients of these two cancers on SEER 65+ incidence rates were estimated. From 2008 to 2015, the algorithm estimated 781 definite CML case patients missed, increasing the number by 10.7%. From 2007 to 2015, the algorithm estimated 4629 definite and 5772 probable bladder case patients missed, increasing the number by 3.8% to 8.1%. Our algorithms offer potential methods for identifying missed case patients and validating the completeness of cancer registries. © 2020 Published by Oxford University Press. This work is written by US Government employees and is in the public domain in the US.

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Characterization of Rare Germline Variants in Familial Multiple Myeloma

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BLOOD 2020年第Sup1期136卷 45-46页

作者： Catalano, Calogerina Blocka, Joanna Huhn, Stefanie Paramasivam, Nagarajan Schlesner, Matthias Weinhold, Niels Sijmons, Rolf Langer, Christian Preuss, Klaus Durie, Brian G. M. Nilsson, Bjorn Goldschmidt, Hartmut Bandapalli, Obul Reddy Hemminki, Kari Forsti, Asta Department of Internal Medicine V Heidelberg University Hospital Heidelberg Germany Division of Molecular Genetic Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany Department of Hematology Oncology and Rheumatology Heidelberg University Hospital Heidelberg Germany Computational Oncology Molecular Diagnostics Program National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg Germany Bioinformatics and Omics Data Analytics German Cancer Research Center (DKFZ) Heidelberg Germany Clinical Cooperation Unit (CCU) Molecular Hematology/Oncology German Cancer Research Center (DKFZ) Heidelberg Germany University Medical Center Groningen University of Groningen Groningen Netherlands Kempten Clinic Kempten Germany Kempten Germany José Carreras Center for Immuno and Gene Therapy Universität Des Saarlandes Homburg/Saar Germany Cedars Sinai Cancer Center Los Angeles CA Division of Hematology and Transfusion Medicine Lund University Lund Sweden National Center for Tumor Diseases Heidelberg Heidelberg Germany Hopp Children's Cancer Center (KiTZ) Heidelberg Germany Heidelberg Germany Division of Pediatric Neurooncology German Consortium for Translational Cancer Research (DKTK) Heidelberg Germany Division of Cancer Epidemiology German Cancer Research Center Heidelberg DEU Faculty of Medicine and Biomedical Center in Pilsen Charles University in Prague Pilsen Czech Republic Pilsen Czech Republic

Introduction: The risk of developing Multiple Myeloma (MM) is 2-4 fold higher in first-degree relatives of patients with MM compared to the general population, suggesting genetic predisposition to this cancer. Indeed, recent genome-wide association studies have identified common risk alleles that predispose for MM. Yet, the impact of these variants on MM risk is too low to explain familial aggregation of MM. High-impact alleles have been identified for other cancers such as ovarian and breast cancer (BRCA1,-2 ) and melanoma (CDKN2A ) but the search for such alleles in MM is still in its infancy. In order to identify high-impact alleles in MM we have performed whole genome/exon sequencing (WGS/WES) in members of MM high risk families. Methods: We included 21 families with multiple cases of MM/MGUS. Whole genome/exome sequencing was performed on a total of 46 affected and 20 unaffected family members. Filtering and prioritization of the variants were performed in accordance with the criteria of our in-house familial cancer variant prioritization pipeline version 2 (FCVPPv2). Loss-of-function variants were further screened using MutPred-LOF, Translate tool and IntOGen/c-BioPortal in order to discriminate pathogenic and neutral variants, to translate a nucleotide sequence to a protein sequence and to visualize the domain affected by the variant and the portion of the protein lost after the newly formed stop codon. Variants were analyzed for predicted effects on splicing by using Human Splicing Finder. Results: We found a total of 148 potentially pathogenic variants, 109 non-synonymous and 39 LOF, in 18 out of 21 MM families. Among our genes, many affect protein metabolism, immune system, and other have known links to carcinogenesis. Additionally, some of them are known to interact with key signaling pathways in MM, including PI3K/Akt/mTOR, Ras/Raf/MEK/MAPK, JAK/STAT, NF-κB, Wnt/β-catenin, and RANK/RANKL/OPG, showing congruency with previously reported literature. Intere

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Comprehensive Comparison of Early Relapse and End-Stage Relapsed Refractory Multiple Myeloma

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BLOOD 2020年第Sup1期136卷 1-1页

作者： Poos, Alexandra M. Giesen, Nicola Catalano, Calogerina Paramasivam, Nagarajan Huebschmann, Daniel John, Lukas Baumann, Anja Hochhaus, Jason Mueller-Tidow, Carsten Sauer, Sandra Huhn, Stefanie Schlesner, Matthias Brors, Benedikt Goldschmidt, Hartmut Raab, Marc S. Weinhold, Niels Department of Internal Medicine V Heidelberg University Hospital Heidelberg Germany Clinical Cooperation Unit (CCU) Molecular Hematology/Oncology German Cancer Research Center (DKFZ) Heidelberg Germany Division of Chromatin Networks German Cancer Research Center (DKFZ) and BioQuant Heidelberg Germany Computational Oncology Molecular Diagnostics Program National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg Germany Department of Pediatric Immunology Hematology and Oncology Heidelberg University Hospital Heidelberg Germany Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH (HI-STEM) Heidelberg Germany Core Center Heidelberg German Cancer Consortium (DKTK) Heidelberg Germany National Center for Tumor Diseases (NCT) Heidelberg Germany Bioinformatics and Omics Data Analytics German Cancer Research Center (DKFZ) Heidelberg Germany Division of Applied Bioinformatics German Cancer Research Center (DKFZ) Heidelberg Germany

Introduction: Treatments incorporating autologous transplantation (ASCT), proteasome inhibitors (PIs), and immunomodulatory drugs (IMIDs) induce deep and durable remissions in most multiple myeloma (MM) patients, resulting in prolonged survival. Yet, patients who suffer from early relapse within 2 years of treatment initiation or become refractory to PIs and IMIDs still have a dismal outcome. The mutational landscape in early relapsed MM (ERMM) and relapsed/refractory MM (RRMM) has been comprehensively described. Several aberrations are associated with these two types of high-risk disease but little is known about the biological difference between them. To this end, we have comparatively and sequentially analyzed whole genome and RNA sequencing data from ERMM and RRMM patients. Methods: We included 32 patients who had relapsed within 2 years of first-line therapy (ERMM group, 30 after ASCT). Samples were collected at first relapse. Paired baseline samples were available from 17 patients. For the RRMM group, we included 43 patients with a median of 5 prior lines of therapy (range 2 - 13; 88% with ASCT), who had relapsed after PIs and IMiDs. For 22 of them consecutive tumor samples were available. Sequencing data were pre-processed using in-house pipelines. Mutations, indels, translocations, and copy number variants were called using Platypus, SOPHIA and ACESeq. Mutational signatures were identified with MMSig and subclonal structures with SciClone. Differential gene expression was assessed using DESeq, gene set enrichment analysis was performed with hypeR, and gene fusions were detected with Arriba. Results: Nonsynonymous mutations occurred more frequently in RRMM (median=180) compared to ERMM at first relapse (median=62, p<0.001). While TP53 mutations were more often seen in ERMM (31% of cases vs. 21% in RRMM), NRAS mutations were enriched in RRMM (37% vs. 22%). Bi-allelic inactivation of TP53 , RB1 , or CDKN2C was more frequent in ERMM (44% vs. 30% in RRMM). In 11/

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Phase Ii Study of Carboplatin/Etoposide Plus Ly2510924, a Cxcr4 Peptide Antagonist, Versus Carboplatin/Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer (Sclc)

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Annals of oncology 2014年 25卷 iv514-iv514页

作者： D.R. Spigel R.W. Weaver M. McCleod O. Hamid J.R. Stille J. Polzer S. Roberson R. Salgia Lung Cancer Research Program Sarah Cannon Research Institute Nashville TN USA Medical Oncology Florida Cancer Specialists St. Petersburg FL USA Medical Oncology Florida Cancer Specialists Fort Myers FL USA Oncology Eli Lilly and Company Indianapolis IN USA Chorus Eli Lilly and Company Indianapolis IN USA Advanced Analytics - Data Mining Eli Lilly and Company Indianapolis IN USA Dept. of Medicine The University of Chicago Medical Centre Chicago IL USA

Aim : LY2510924, an antagonist to the chemokine receptor CXCR4, inhibits tumor growth and metastasis in xenograft models. A Phase I trial with LY2510924 demonstrated an acceptable safety profile with a robust pharmacodynamic profile. This open-label phase II trial evaluated the clinical benefit of carboplatin/etoposide plus LY2510924 versus carboplatin/etoposide, the standard of care (SOC), as a first-line therapy in patients (pts) with extensive-stage SCLC. Methods : Treatment-naïve extensive-stage SCLC pts were randomized 1:1 to receive six 21-day cycles of either LY+SOC (Arm A) or SOC (Arm B). A 20-mg dose of LY2510924 was self-administered by the patient subcutaneously on days 1-7 of each cycle. Efficacy was evaluated using RECIST v. 1.1; adverse events were evaluated using MedDRA v. 14.0. The primary end point, progression-free survival (PFS), was analyzed using a stratified log-rank test. Secondary end points were objective response rate (ORR), duration of overall response (DoR), overall survival (OS), and safety. Results : Median follow-up time was 8.4 months. Pt characteristics were comparable in Arm A (N=47) and Arm B (N=43). Median PFS for Arm A was 5.88 months (95% confidence interval 4.83, 6.24) and Arm B 5.85 months (4.63, 6.51), p=0.9806. ORRs were 74.5% and 81.0%; median DoR were 4.83 months (3.58, 5.09) and 4.67 months (3.32, 5.78) for Arms A and B, respectively. The median OS was 9.72 months (6.64, 11.70) and 11.14 months (8.25, 13.44), p=0.1120 for Arms A and B, respectively. Grade 3/4 treatment-emergent adverse events>8% in Arm A included neutrophil count decrease (40% vs. 56%), anemia (30% vs. 33%), platelet count decrease (23% vs. 16%), lung infection (11% vs. 0%), white blood cell count decrease (9% vs. 9%), and febrile neutropenia (9% vs. 2%) (Arm A vs. Arm B). No pts died due to adverse events. Conclusions : No improvements in PFS, ORR, DoR, or OS in treatment-naïve extensive-stage SCLC pts were observed when LY2510924 was added to SOC. The a

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Embolize, supercharge, resect: Embolization to enhance hepatic vascularization prior to en-bloc pancreas and arterial resection

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Cirugia espanola 2024年第12期102卷 633-641页

作者： Juli Busquets Luis Secanella Thiago Carnaval Maria Sorribas Mónica Serrano-Navidad Esther Alba Elena Escalante Sandra Ruiz-Osuna Núria Peláez Juan Fabregat Department of Hepatobiliary and Pancreatic Surgery Hospital Universitari de Bellvitge Research Group of Hepato-biliary and Pancreatic Diseases Institut d'Investigació Biomèdica de Bellvitge - IDIBELL L'Hospitalet de Llobregat Barcelona Spain Departament de Ciències Clíniques Facultat de Medicina i Ciències de la Salut Universitat de Barcelona (UB) Barcelona Spain. Electronic address: jbusquets@bellvitgehospital.cat. Departament d'Infermeria Fonamental i Medicoquirúrgica Facultat de Medicina i Ciències de la Salut Universitat de Barcelona (UB) Barcelona Spain. Pharmacology Unit Department of Pathology and Experimental Therapeutics School of Medicine and Health Sciences IDIBELL University of Barcelona Bellvitge Campus L'Hospitalet de Llobregat Barcelona Spain Oncology Data Analytics Program (ODAP) Catalan Institute of Oncology IDIBELL L'Hospitalet de Llobregat Barcelona Spain. Department of Hepatobiliary and Pancreatic Surgery Hospital Universitari de Bellvitge Research Group of Hepato-biliary and Pancreatic Diseases Institut d'Investigació Biomèdica de Bellvitge - IDIBELL L'Hospitalet de Llobregat Barcelona Spain. Radiology Department Hospital Universitari de Bellvitge L'Hospitalet de Llobregat Barcelona Spain.

INTRODUCTION:Embolization could increase the resectability of pancreatic tumors by supercharging visceral arterial perfusion prior to pancreatic surgery with arterial en-bloc resection. Its indications, however, are controversial. METHODS:We retrospectively analyzed the results of a single-center database of patients undergoing pancreatic surgery with arterial resection (AR) after preoperative arterial embolization (PAE) to increase hepatic vascular flow and spare arterial reconstruction. RESULTS:PAE was planned in 15 patients with arterial involvement due to pancreatic tumors. Three patients were excluded due to the finding of irresectable disease during surgery. Twelve cases were resected because of pancreatic cancer (10), distal cholangiocarcinoma (1), and pancreatic neuroendocrine tumor (1). Arterial involvement in these cases required embolization of the substitute right hepatic artery (RHA) (5), left hepatic artery (1), and common hepatic artery (CHA) (6) to enhance liver vascularization. Two patients presented migration of the vascular plug after PAE. Six pancreatoduodenectomies and 6 distal pancreatectomies were performed, the latter associated with en-bloc celiac trunk and CHA resection. R0 was achieved in 7 out of 12 patients, and pathological vascular involvement was confirmed in 8. Postoperative complications included one patient who developed gastric ischemia and underwent gastrectomy, and one patient who underwent reoperation for acute cholecystitis with liver abscesses. CONCLUSION:Preoperative arterial embolization before pancreatic surgery with hepatic arterial resection enables surgeons to precondition hepatic vascularization and prevent hepatic ischemia. In addition, this avoids having to perform arterial anastomosis in the presence of pancreatic suture.

关键词： Embolización Embolization Neoplasias pancreáticas Pancreatic neoplasms Procedimientos quirúrgicos Surgical procedures

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