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Leukocyte driven-decidual angiogenesis in ***

Cellular & Molecular Immunology 2014年第6期11卷 522-537页

作者： patricia da lima Jianhong Zhang Caroline Dunk Stephen J Lye B Anne Croy Ottawa Hospital Research Institute The Ottawa Hospital General Campus Critical Care Wing Ottawa ON Canada Research Centre for Women's and Infants' Health Lunenfeld-Tanenbaum Research Institute Mount Sinai Hospital Toronto ON Canada Department of Physiology and University of Toronto Toronto ON Canada Department of Obstetrics and Gynecology University of Toronto Toronto ON Canada Department of Biomedical and Molecular Sciences Queen's University Kingston ON Canada

Successful pregnancy and long-term, post-natal maternal and offspring cardiac, vascular and metabolic health require key maternal cardiovascular adaptations over gestation. Within the pregnant decidualizing uterus, coordinated vascular, immunological and stromal cell changes occur. Considerable attention has been given to the roles of uterine natural killer （uNK） cells in initiating decidual spiral arterial remodeling, a process normally completed by mid-gestation in mice and in humans. However, leukocyte roles in much earlier, region specific, decidual vascular remodeling are now being defined. Interest in immune cell-promoted vascular remodeling is driven by vascular aberrations that are reported in human gestational complications such as infertility, recurrent spontaneous abortion, preeclampsia （PE） and fetal growth restriction. Appropriate maternal cardiovascular responses during pregnancy protect mothers and their children from later cardiovascular disease risk elevation. One of the earliest uterine responses to pregnancy in species with hemochorial placentation is stromal cell decidualization, which creates unique niches for angiogenesis and leukocyte recruitment. In early decidua basalis, the aspect of the implantation site that will cradle the developing placenta and provide the major blood vessels to support mature placental functions, leukocytes are greatly enriched and display specialized properties. UNK cells, the most abundant leukocyte subset in early decidua basalis, have angiogenic abilities and are essential for normal early decidual angiogenesis. The regulation of uNK cells and their roles in determining maternal and progeny cardiovascular health over ore^nancv and PostPartum are discussed.

关键词： angiokines blood vessel decidua endometrium natural killer cell receptors uterine natural killer cell

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Ly49 receptors activate angiogenic mouse DBA＋ uterine natural killer cells

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Cellular & Molecular Immunology 2014年第5期11卷 467-476页

作者： patricia da lima Megan M Tu Mir Munir A Rahim Annie R Peng B Anne Croy Andrew P Makrigiannis Department of Biochemistry Microbiologyand Immunology University of Ottawa Ottawa ON KIN 6N5 Canada Biomedical and Molecular Sciences Queen's University Kingston ON K7L 3N6 Canada

In humans, specific patterns of killer immunoglobulin-like receptors （KIRs） expressed by uterine natural killer （uNK） cells are linked through HLA-C with pregnancy complications （infertility, recurrent spontaneous abortion, intrauterine growth restriction and preeclampsia）. To identify mechanisms underpinning the associations between NK cell activation and pregnancy success, pregnancies were studied in mice with genetic knockdown （KD） of the MHC-activated Ly49 receptor gene family. ***49KD pregnancies were compared to normal control ***49z29 and C57BL/6 （B6） pregnancies. At mid-pregnancy （gestation day （gd9.5））, overall uNK cell （TCRI^-CD122＋DBA＋DX5- （DBA＋DX5-）） and TCRIβ-CD122＋DBA-DX5＋（DBA-DX5＋）） frequencies in pregnant uterus were similar between genotypes. Ly49KD lowered the normal frequencies of Ly49＋ uNK cells from 90.3% to 47.8% in DBA-DX5＋ and 78.8% to 6.3% in DBA＋DX5- uNK cell subtypes. ***49KD matings frequently resulted in expanded blastocysts that did not implant （subfertility）. ***49KD mice that established pregnancy had gestational lengths and litter sizes similar to controls. ***49KD neonates, however, were heavier than controls. ***49KD implantation sites lagged in early （gd6.5） decidual angiogenesis and were deficient in mid-pregnancy （gd 10.5） spiral arterial remodelling. Ultrastructural analyses revealed that ***49KD uNK cells had impaired granulogenesis, while immunocytochemistry revealed deficient vascular endothelial cell growth factor （VEGFA） production. Perforin and IFNG expression were normal in ***49KD uNK cells. Thus, in normal mouse pregnancies, Ly49 receptor signaling must promote implantation, early decidual angiogenesis and mid-pregnancy vascular remodelling. Disturbances in these functions may underlie the reported genetic associations between human pregnancy complications and the inability of specific conceptus MHCs to engage activating KIR on uNK cells.

关键词： fetal growth deviation granule biogenesis MHC-I receptors uterine natural killer cells vascular endothelialcell growth factor

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Differential diagnosis between autism spectrum disorder and other developmental disorders with emphasis on the preschool period

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世界儿科杂志:英文版 2023年第8期19卷 715-726页

作者： Taynara Amancio de lima patricia Aparecida Zuanetti Marina Estima Neiva Nunes Ana Paula Andrade Hamad Department of Neurosciences and Behavioral Sciences Ribeirão Preto Medical SchoolUniversity of São PauloAv.Bandeirantes3900Monte AlegreRibeirão PretoSP14049-900Brazil University Hospital Ribeirão Preto Medical SchoolUniversity of São Paulo(HCFMRP-USP)Ribeirão PretoSPBrazil

Background Neurodevelopmental disorders are a heterogeneous group of conditions that manifest as delays or deviations in the acquisition of expected developmental milestones and behavioral *** spectrum disorder(ASD)is a neurodevelopmental disorder characterized by deficits in communication and social interaction and by repetitive and restricted patterns of behavior,interests and *** aim of this review is to discuss the clinical features of the differential diagnoses of ASD that are prevalent among preschoolers,focusing on their similarities and *** sources The international medical literature search was conducted using PubMed and was revised regarding the subject using single and/or combined keywords as follows:differential diagnosis,preschoolers,diagnostic challenge,attention deficit hyperactivity disorder,intellectual disability,high abilities/giftedness,childhood apraxia of speech,social communication disorder,Landau–Kleffner syndrome,stereotyped movement disorder and excessive screen *** We describe conditions commonly found in clinical practice,taking ASD as a *** addressed converging and divergent aspects of behavior,cognition,communication,language,speech,socialization,and stereotypes for the diagnosis of ASD and other disorders identified as potential differential or comorbid *** The ranking and characterization of symptoms appear to be essential for better understanding the underlying common ground between children with developmental disorders and children with ASD,thus properly diagnosing and directing social,professional,or medication *** detailed discussion adds to the literature since,although ASD differential diagnoses are frequently mentioned and discussed in textbooks and journal articles,they rarely occupy a prominent place as we aimed herein.

关键词： Autism spectrum disorder Clinical features Differential diagnosis Neurodevelopmental disorders Preschool

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Roots and rhizomes of wild Asparagus:Nutritional composition,bioactivity and nanoencapsulation of the most potent extract

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Food Bioscience 2022年第1期45卷 349-360页

作者： Khaoula Adouni Ana Júlio Celestino Santos-Buelga Ana M.Gonzalez-Paramas Patrícia Filipe patricia Rijo Sofia A.Costa lima Salette Reis Angela Fernandes Isabel C.F.R.Ferreira Virginia Fernandez-Ruiz patricia Morales Guido Flamini Lotfi Achour Pedro Fonte Laboratoire de Recherche“Bioressources:Biologie Integrative&Valorisation” Institut Superieur de Biotechnologie de MonastirAvenue Tahar HaddedBP 74Universite de Monastir5000MonastirTunisia CBIOS-Research Center for Biosciences&Health Technologies Universidade Lusofona de Humanidades e TecnologiasCampo Grande 3761749-024LisbonPortugal Department of Biomedical Sciences University of Alcal´aCtra.Madrid-Barcelona Km.33.60028871Alcala de HenaresMadridSpain Grupo de Investigacion en Polifenoles(GIP-USAL) Facultad de FarmaciaUniversidad de SalamancaCampus Miguel de UnamunoE-37007SalamancaSpain Research Institute for Medicines(iMed.ULisboa) Faculty of PharmacyUniversidade de LisboaAv.Professor Gama Pinto1649-003LisboaPortugal LAQV REQUIMTEDepartment of Chemical Sciences–Applied Chemistry LabFaculty of Pharmacy10 University of PortoRua Jorge de Viterbo Ferreira 2284050-313PortoPortugal Centro de Investigacao de Montanha(CIMO) Instituto Politecnico de BragancaCampus de Santa Apolonia5300-253BragancaPortugal Department of Nutrition and Food Science Faculty of PharmacyComplutense University of Madrid(UCM)Plaza Ramon y Cajal s/n28040MadridSpain Dipartimento di Farmacia University of Pisavia Bonanno 656126PisaItaly Centro Interdipartimentale di Ricerca“Nutraceutica e Alimentazione per la Salute”University of Pisa Via del Borghetto 8056124PisaItaly Center for Marine Sciences(CCMar) University of AlgarveGambelas Campus8005-139FaroPortugal Department of Chemistry and Pharmacy Faculty of Sciences and TechnologyUniversity of AlgarveGambelas Campus8005-139FaroPortugal iBB-Institute for Bioengineering and Biosciences Department of BioengineeringInstituto Superior TecnicoUniversidade de Lisboa1049-001LisboaPortugal Associate Laboratory i4HB—Institute for Health and Bioeconomy at Instituto Superior Tecnico Universidade de LisboaAv.Rovisco Pais1049-001LisboaPortugal

The nutritional composition and bioactive properties of roots and rhizomes of Asparagus stipularis were *** activity of extracts obtained by infusion was evaluated using free radicals scavenging and reducing power *** liver primary cell was used to check the hepatotoxicity of *** revealed that Asparagus samples are likely a source of nutrients,such as dietary fibre and essential fatty ***-daD-ESI/MS characterization of infusions allowed the identification and quantitation of 7 phenolic compounds,all hydroxycinnamoyl derivatives,with caffeic acid as the most *** infusion contained the highest amounts of these *** also exhibited the highest antioxidant activity in all assays,with EC_(50) values of 0.44±0.01,0.98±0.03 and 0.64±0.01 mg/mL for DPPH,ABTS and FRAP assays,respectively,with no toxicity towards PLP2 primary cell cultures(GI_(50)>400μg/mL).PLGA nanoparticles loaded with root extract were prepared using solvent-evaporation double emulsion *** size was about 260 nm and a polydispersity index around 0.1,with a zeta potential of about-36 mV,as well as a good encapsulation efficiency of approximately 83%.Their morphology was analysed by SEM and spherical polymeric nanoparticles with a smooth surface were *** and DSC were also performed,which allowed corroborating the efficacy of the encapsulation and to confirm the production of a stable and robust system to load Asparagus *** developed nanoparticles are expected to be used as delivery systems for bioactive compounds of *** and they could be used as an innovative dietary supplement.

关键词： Asparagus stipularis Nutritional composition Antioxidant activity Nanoparticles PLGA

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Anti-Candida and anti-Cryptococcus evaluation of 15 non-alkaloidal compounds from Pterogyne nitens

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Asian Pacific Journal of Tropical Biomedicine 2016年第10期6卷 841-845页

作者： Caroline Sprengel lima Carlos Roberto Polaquini Mariana Bastos dos Santos Fernanda patricia Gullo Fernanda Sangalli Leite Liliane Scorzoni Vanderlan da Silva Bolzani Maria Jose Soares Mendes-Giannini Ana Marisa Fusco-Almeida Andréia Alves Rezende Luis Octavio Regasini Laboratory of Green and Medicinal Chemistry Department of Chemistry and Environmental Sciences Institute of Biosciences Letters and Exact Sciences Sao Paulo State University (UNESP) Department of Clinical Analysis School of Pharmaceutical Sciences Sao Paulo State University (UNESP) Department of Organic Chemistry Institute of Chemistry Sao Paulo State University (UNESP) Department of Biology and Animal Sciences Faculty of Engineering Sao Paulo State University (UNESP)

Objective: To evaluate anti-Candida and anti-Cryptococcus activities of 15 nonalkaloidal compounds from Pterogyne nitens Tulasne(Leguminosae), a South American medicinal ***: Compounds were submitted to antifungal assays, using microdilution method described by Clinical and Laboratory Standards Institute document, with minor modifications. Five species of Candida and two species of Cryptococcus, including clinical isolates were screened. Antifungal activity was expressed by minimum inhibitory concentration(MIC). Amphotericin B and fluconazole were used as standard antifungal ***: Among tested compounds, six substances presented fungal growth inhibition(MIC da glabrata ATCC 90030, Cryptococcus gattii 118 and fluconazole-resistant clinical isolate of Cryptococcus neoformans var. grubii. Pedalin(2) and nitensoside B(3), two glycosylated flavone derivatives, were active against Cryptococcus neoformans ATCC 90012(MIC = 7.80 mg/m L).Conclusions: Flavone derivatives from Pterogyne nitens can serve as prototypes for the design and development of innovative anti-Candida and anti-Cryptococcus hits.

关键词： Candida Cryptococcus Antifungal Pterogyne nitens Flavonoid Opportunistic fungi

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Inhibition of BACE1, the β-secretase implicated in Alzheimer’s disease, by a chondroitin sulfate extract from Sardina pilchardus

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Neural Regeneration Research 2020年第8期15卷 1546-1553页

作者： Courtney J.Mycroft-West Anthony J.Devlin Lynsay C.Cooper patricia Procter Gavin J.Miller david G.Fernig Marco Guerrini Scott E.Guimond Marcelo A.lima Edwin A.Yates Mark Andrew Skidmore Molecular&Structural Biosciences School of Life SciencesKeele UniversityHuxley BuildingKeeleStaffordshireST55BGUK Lennard-Jones Laboratory School of Chemical and Physical SciencesKeele UniversityKeeleStaffordshireST55BGUK Department of Biochemistry Institute of Integrative BiologyUniversity of LiverpoolCrown StreetLiverpoolL697ZBUK Istituto di Ricerche Chimiche e Biochimiche G.Ronzoni Via G.Colombo 8120133 MilanItaly School of Medicine KeeleStaffordshireST55BGUK

The pharmaceutical and anticoagulant agent heparin,a member of the glycosaminoglycan family of carbohydrates,has previously been identified as a potent inhibitor of a key Alzheimer’s disease drug target,the primary neuronalβ-secretase,β-site amyloid precursor protein cleaving enzyme 1(BACE1).The anticoagulant activity of heparin has,however,precluded the repurposing of this widely used pharmaceutical as an Alzheimer’s disease ***,a glycosaminoglycan extract,composed predominantly of 4-sulfated chondroitin sulfate,has been isolated from Sardina pilchardus,which possess the ability to inhibit BACE1(IC50[half maximal inhibitory concentration]=4.8μg/mL),while displaying highly attenuated anticoagulant activities(activated partial thromboplastin time EC50[median effective concentration]=403.8μg/mL,prothrombin time EC50=1.3 mg/mL).The marine-derived,chondroitin sulfate extract destabilizes BACE1,determined via differential scanning fluorimetry(ΔTm–5°C),to a similar extent as heparin,suggesting that BACE1 inhibition by glycosaminoglycans may occur through a common mode of action,which may assist in the screening of glycan-based BACE1 inhibitors for Alzheimer’s disease.

关键词： amyloid-β aspartyl protease carbohydrates galactosaminoglycans heparan sulfate heparin marine polysaccharide pilchards sardines therapeutics

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Brazilian biosafety law and the new breeding technologies

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Frontiers of Agricultural Science and Engineering 2020年第2期7卷 204-210页

作者： Alexandre lima NEPOMUCENO Renata FUGANTI-PAGLIARINI Maria Sueli Soares FELIPE Hugo Bruno Correa MOLINARI Edivaldo Domingues VELINI Eduardo Romano de Campos PINTO Maria Lucia Zaidan daGLI Galdino ANDRADE FILHO patricia Machado Bueno FERNANDES Embrapa Soybean Londrina 86001970Brazil Catholic University of Brasilia Brasilia 70790160Brazil Embrapa Agroenergy Biological Station ParkBrasilia 70770901Brazil Paulista State University Julio de Mesquita Filho Botucatu Faculty of Agronomic SciencesBotucatu 18610307Brazil Embrapa Biotechnology and Genetic Resources—Biological Station Park Brasilia 70770900Brazil Sao Paulo University Veterinary FacultySao Paulo 05508900Brazil Londrina State University Microbiology DepartmentUniversity CampusLondrina 86051990Brazil Espirito Santo Federal University Biotechnology Post GraduationVitoria 29040090Brazil CTNBio(National Biosafety Technical Commission) Brasilia 70610200Brazil

Globally,the area of land cultivated with genetically modified(GM)crops has increased a thousand-fold over the last two *** this technology has become important for food production,the regulatory frameworks that underpin these outcomes are based on a list of requirements for a risk assessment that differ from country to *** recent years,policymakers have had the opportunity to learn from the controversies over transgenics to create effective regulatory milestones for emerging technologies,allowing them to reach their potential for a more sustainable agriculture,ensuring food *** Brazil,Law No.11.105 of 24 March 2005 established a framework with four main organizations responsible for risk assessment and ***,most of new breeding technologies did not exist at that time and were not considered in this ***2016,Normative Resolution No.16 of the National Biosafety Technical Commission(CTNBio)was established to address this gap based on the evaluation of the products obtained through these techniques(termed Innovative Precision Improvement Techniques in the resolution),in a case-by-case consultation ***,if the product is designated to be a GM,the developer will have to go through the biosafety requirements and will be approved only after CTNBio risk *** the product is designated not to be GM(for the purposes of the legislation),then it can be registered using the existing ***,152 GM products are commercially approved in *** 2018,CTNBio assessed the first consultation on commercial release of plants generated using the new breeding technologies and has subsequently approved six *** is expected that many institutions would be able to participate in Brazilian and world markets,developing and introducing new biotechnological solutions and products through a more sustainable approach and without facing public disapproval,a common issue for GM crops.

关键词： Brazilian legislation CTNBio genetically modified crops

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Tako-Tsubo Cardiomyopathy—The Role of Physical and Emotional Stressors:Two Case Report

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International Journal of Clinical Medicine 2012年第2期3卷 145-150页

作者： Patrícia Margarida Serra Carvalho Jandira Helena lima Joao Bernardo Cunha patricia Gloria Dinis Dias Jose Goncalo Diniz Vieira Jose Manuel Nascimento Costa Internal Medicine Ward Coimbra University HospitalCoimbraPortugal

Introduction: Tako-Tsubo cardiomyopathy describes a form of acute and reversible left ventricular dysfunction with a clinical presentation, ECG and cardiac biomarkers that makes it indistinguishable from acute coronary syndrome. Case Presentation: The authors present two cases of tako-tsubo cardiomyopathy in postmenopausal women, the first case following an emotional stressful event and a second case following a blood transfusion and probably associated with intravenous catecholamine perfusion. Both had unobstructed coronary arteries and regional wall-motion abnormalities typical of this syndrome. Conclusions: Tako-tsubo cardiomyopathy is a condition often misdiagnosed. A clinical presentation suggestive of acute coronary syndrome in a postmenopausal woman without history of coronary disease and in whom a precipitating stressful event can be found should lead the physician to suspect the diagnosis of tako-tsubo cardiomyopathy. This syndrome associated with blood transfusion has rarely been described.

关键词： Tako-Tsubo Left Ventricle Postmenopausal Stress

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Immunotherapy in triple-negative breast cancer:A literature review and new advances

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World Journal of Clinical Oncology 2022年第3期13卷 219-236页

作者： Guillermo Arturo Valencia patricia Rioja Zaida Morante Rossana Ruiz Hugo Fuentes Carlos A Castaneda Tatiana Vidaurre Silvia Neciosup Henry L Gomez Department of Medical Oncology Instituto Nacional de Enfermedades NeoplásicasLima 15036Peru

Triple-negative breast cancer(TNBC)is a highly complex,heterogeneous disease and historically has limited treatment *** has a high probability of disease recurrence and rapid disease progression despite adequate systemic *** has emerged as an important alternative in the management of this malignancy,showing an impact on progression-free survival and overall survival in selected *** this review we focused on immunotherapy and its current relevance in the management of TNBC,including various scenarios(metastatic and early-neoadjuvant,adjuvant-),new advances in this subtype and the research of potential predictive biomarkers of response to treatment.

关键词： Triple-negative breast cancer Early disease Immunotherapy Biomarkers Metastatic disease

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Survival after curative pancreaticoduodenectomy for ampullary adenocarcinoma in a South American population:A retrospective cohort study

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World Journal of Gastrointestinal Surgery 2022年第1期14卷 24-35页

作者： Ramiro Manuel Fernandez-Placencia Paola Montenegro Melvy Guerrero Mariana Serrano Emperatriz Ortega Mercedes Bravo Lourdes Huanca Stéphane Bertani Juan Manuel Trejo patricia Webb Jenny Malca-Vasquez Luis Taxa Alberto Lachos-davila Juan Celis-Zapata Carlos Luque-Vasquez Eduardo Payet Eloy Ruiz Francisco Berrospi Hepato-Pancreato-Biliary Section Department of Abdominal SurgeryInstituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru International Joint Laboratory of Molecular Anthopological Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Unite Pharmacochim&Pharmacol Dev UMR152F-31062 ToulouseFrance Department of Radiation Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Abdominal Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru

BACKGROUND Ampullary adenocarcinoma(AAC)is a rare neoplasm that accounts for only 0.2%of all gastrointestinal *** incidence rate is lower than 6 cases per million *** prognostic factors have been described for AAC and are associated with a wide range of survival ***,these studies have been exclusively conducted in patients originating from Asian,European,and North American *** To evaluate the histopathologic predictors of overall survival(OS)in South American patients with AAC treated with curative pancreaticoduodenectomy(PD).METHODS We analyzed retrospective data from 83 AAC patients who underwent curative(R0)PD at the National Cancer Institute of Peru between January 2010 and October 2020 to identify histopathologic predictors of *** Sixty-nine percent of patients had developed intestinal-type AAC(69%),23%had pancreatobiliary-type AAC,and 8%had other ***-one percent of patients were classified as Stage I,according to the AJCC 8 th *** occurred primarily in the liver(n=8),peritoneum(n=4),and lung(n=4).Statistical analyses indicated that T3 tumour stage[hazard ratio(HR)of 6.4,95%confidence interval(CI)of 2.5-16.3,P<0.001],lymph node metastasis(HR:4.5,95%CI:1.8-11.3,P=0.001),and pancreatobiliary type(HR:2.7,95%CI:1.2-6.2,P=0.025)were independent predictors of *** Extended tumour stage(T3),pancreatobiliary type,and positive lymph node metastasis represent independent predictors of a lower OS rate in South American AAC patients who underwent curative PD.

关键词： Gastrointestinal neoplasms Adenocarcinoma Ampulla Pancreaticoduodenectomy Survival South America

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