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New avenues for the treatment of immunotherapy-resistant pancreatic cancer

World Journal of Gastrointestinal Oncology 2024年第4期16卷 1134-1153页

作者： luis Guilherme de Oliveira Silva Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Mariana dos Santos Calmon gabriel Lima Correa Santos gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy

关键词： Pancreatic cancer Immunotherapy Resistance Tumor microenvironment manipulation Combined immunotherapy

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Fluidization of binary mixtures of sisal residue and sand:A new model for deriving the final fluidization velocity

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Particuology 2018年第5期16卷 10-22页

作者： David Vasconcelos gabriele Batalha luis gabriel pereira Carlos Augusto Pires Chemical Reaction Engineering Laboratory Federal University of Bahia40.210-910SalvadorBABrazil

The influence of different factors on the fiuidization of a binary mixture of sisal residue and sand was investigated.The particle sizes of the sand and sisal residue were varied from 0.2to 0.8mm and the biomass mass fractions from 2% to 9%.Some segregation was noted,and a significant relationship was found among the final fluidization velocity (Uff),the biomass and sand sizes,and the biomass mass fraction.A novel model was developed for predicting Uff,leading to an average discrepancy of 12.69% between the measured and predicted Uff compared with the best match of 15.32% when using a model from a previous paper.The new model was applied to data from studies using other biomass and a broad range of particle characteristics.The average divergences from measured values when using the new model were 7.9% for corn cob and walnut shell,and 20.5% for sweet sorghum bagasse,tobacco residue, and soy hulls.These were superior to the values derived using other models.Our results confirm the accuracy of the model developed in this work and show that it represents a viable alternative way to calculate Uff for a binary mixture of sand and biomass.

关键词： Fluidization Binary mixture Sisal residue Final fluidization velocity model

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Immune pathway through endometriosis to ovarian cancer

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World Journal of Clinical Oncology 2024年第4期15卷 496-522页

作者： Mariana Santos Calmon Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro luis Guilherme de Oliveira Silva gabriel Lima Correa Santos gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

关键词： Ovarian neoplasms Endometriosis Endometriosis-associated ovarian cancers Immune response Immunotherapy

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From liver to hormones:The endocrine consequences of cirrhosis

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World Journal of Gastroenterology 2024年第9期30卷 1073-1095页

作者： Juan Eduardo Quiroz-Aldave Elman Rolando Gamarra-Osorio María del Carmen Durand-Vásquez Luciana del Pilar Rafael-Robles Jhean gabriel Gonzáles-Yovera María Alejandra Quispe-Flores luis Alberto Concepción-Urteaga Alejandro Román-González José Paz-Ibarra Marcio José Concepción-Zavaleta Non-communicable Diseases Endocrinology Research LineHospital de Apoyo ChepénChepén 13871Peru Department of Endocrinology Hospital Víctor Lazarte EchegarayTrujillo 13006Peru Department of Endocrinology Clínica Javier PradoLima 15046Peru Department of Gastroenterology Hospital Nacional Guillermo Almenara IrigoyénLima 15018Peru Department of Endocrinology Hospital de Emergencias GrauLima 15001Peru Internal Medicine Hospital Regional Docente de TrujilloTrujillo 13011Peru Department of Endocrinology Hospital Universitario de San Vicente FundaciónMedellin 050010Colombia Internal Medicine Universidad de AntioquiaMedellín 050010Colombia School of Medicine Universidad Nacional Mayor de San MarcosLima 15081Peru Department of Endocrinology Hospital Nacional Edgardo Rebagliati MartinsLima 15072Peru Carrera de Medicina Humana Universidad Científica del SurLima 15067Peru

Hepatocrinology explores the intricate relationship between liver function and the endocrine system.Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption.Despite its importance,assessing endocrine issues in cirrhotic patients is frequently neglected.This article provides a comprehensive review of the epidemiology,pathophysiology,diagnosis,and treatment of endocrine disturbances in liver cirrhosis.The review was conducted using the PubMed/Medline,EMBASE,and Scielo databases,encompassing 172 articles.Liver cirrhosis is associated with endocrine disturbances,including diabetes,hypoglycemia,sarcopenia,thyroid dysfunction,hypogonadotropic hypogonadism,bone disease,adrenal insufficiency,growth hormone dysfunction,and secondary hyperaldosteronism.The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system,respectively.Sarcopenia can be assessed through imaging and functional tests,while other endocrine disorders are evaluated using hormonal assays and imaging studies.Treatment options include metformin,glucagon-like peptide-1 analogs,sodium-glucose co-transporter-2 inhibitors,and insulin,which are effective and safe for diabetes control.Established standards are followed for managing hypoglycemia,and hormone replacement therapy is often necessary for other endocrine dysfunctions.Liver transplantation can address some of these problems.

关键词： Diabetes mellitus Hypoglycemia Thyroid diseases Hypogonadism Metabolic bone diseases Liver cirrhosis

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Sarcopenia and Anemia Are Predictors of Poor Prognostic in Cervical Cancer Patients

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Open Journal of Obstetrics and Gynecology 2024年第5期14卷 693-704页

作者： Leandro Santos de Araujo Resende Francine Vilela de Amorim Miguel Soares Conceição Rodrigo Menezes Jales Patrick Nunes pereira luis Otávio Sarian Glauco Baiocchi Sophie Derchain Agnaldo Lopes da Silva Filho Department of Gynecology and Obstetrics Botucatu Medical School S&#227o Paulo State University UNESP S&#227o Paulo Brazil Department of Health Sciences University of Sao Francisco S&#227o Paulo Brazil Department of Obstetrics and Gynecology School of Medical Science State University of Campinas (UNICAMP) Campinas Brazil Department of Gynecologic Oncology AC Camargo Cancer Center Sao Paulo Brazil Department of Gynecology and Obstetrics School of Medicine of the Federal University of Minas Gerais Belo Horizonte Brazil

Objective: Evaluate pretreatment sarcopenia and anemia as prognostic factors in women undergoing treatment for cervical cancer (CC) with concurrent chemoradiotherapy (CCRT). Methods: 151 women with CC were analysed in this cohort study. Pretreatment computed tomography (CT) images were analysed to assess skeletal muscle index (SMI). Hazard ratios (HR) and multivariate Cox proportional HR were used to analyse association between low SMI, age, body mass index (BMI), haemoglobin levels, histological type, and International Federation of Gynaecology and Obstetrics (FIGO) stage with PFS and OS. Results: A total of 151 patients were included, 53 (35.1%) presented pretreatment sarcopenia;51 (34%) stage I/II and 100 (66%) stage III/IV. Among those patients in advanced stage (III/IV) 37 (70%) (p = 0.28) were sarcopenic at the beginning of treatment. Sarcopenia was associated with worse progression-free survival (PFS) and overall survival (OS) in our cohort [HR 0.97 (p = 0.01)] [HR 0.73 (p = 0.001)], as well as anemia [HR 0.73 (p = 0.001)] [HR 0.78 (p = 0.001)]. Linear regression models indicated that despite showing no association with age, neutrophil or platelet counts, sarcopenia was associated with pretreatment anemia levels (p = 0.01). After a multivariate analysis, only haemoglobin (anemia) and complete CCRT remained associated with PFS and OS. Sarcopenia and anemia were associated with worse PFS and OS in FIGO stage I/II. Conclusion: Pretreatment sarcopenia was significantly associated with low haemoglobin levels. Anemia and incomplete CCRT were independently associated with poor prognosis in women with CC. Pretreatment sarcopenia, as low SMI, was a predictor of poor prognostic in early stages of CC.

关键词： Cervical Cancer Sarcopenia Anemia Chemoradiotherapy

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Clinical/Behavioral Monitoring of Rodents and Rabbits Undergoing Scientific Experiments

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Open Journal of Veterinary Medicine 2024年第5期14卷 91-109页

作者： Luiz Cesar Cavalcanti pereira Jhônata Willy Rocha Coelho Hyago da Silva Medeiros Elidio Rita de Cássia dos Passos Ferraz Da Silva João gabriel Regis Sobral Bárbara Alves de Brito Soledade Leandro Thomaz Vilela Isabele Barbieri Dos Santos Institute of Science and Technology in Biomodels (ICTB) Oswaldo Cruz Foundation (FIOCRUZ) Rio de Janeiro Brazil Laboratory Animal Facility of the Carlos Chagas Pavilion of the Animal Experimentation Center (CEA) Oswaldo Cruz Institute (IOC) Oswaldo Cruz Foundation (FIOCRUZ) Rio de Janeiro Brazil

Background: We currently have international and national guidelines regarding the assessment and monitoring of clinical signs and humane endpoints in animals used in teaching and research, which make the performance of these activities mandatory for any experiment and professional working in this area. Assigning the severity of a research experiment is the result of an analysis of records of observations of the animal’s behavior, and clinical signs. The aim of this study was to describe the importance of carrying out a severity assessment associated with clinical and behavioral monitoring of rodents and rabbits during experimentation to maintain the welfare of these animals undergoing scientific research. Methods: The literature search was carried out using the following terms: “Monitoring”;“Humane endpoints”;“Animal welfare”, “Rodents”;“Rabbits”, and as connectors “and”;“or”, in the following databases: PubMed;LILACS/BIREME and SciELO. Results: A total of 987 articles were identified in the databases, and 20 of these studies were included in this review. Conclusions: Humane endpoint protocols and procedure severity tables are of the utmost importance, both from an ethical point and to refine the results of research conducted on laboratory animals. They should be drawn up jointly by the teams responsible for the project and the maintenance of the animals during the research period, and the data obtained should be published so that the scientific community can have access to it, helping to disseminate these practices, as well as helping to draw up new procedures. Monitoring and evaluating the welfare and clinical condition of animals undergoing scientific research procedures is the responsibility of the professors, researchers, veterinarians, and animal facility coordinators. The Ethics Committee on the Use of Animals must monitor all the activities conducted with the animals, by inspecting the experimental procedures and the physical environment of the laboratory animal facility where the animals are housed.

关键词： Monitoring Humane Endpoints Animal Welfare Experimental Design Laboratory Animals’ Investigations

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Disaster Journalism in Print Media:Analysis of the Top 10 Hydrogeomorphological Disaster Events in Portugal,1865–2015

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International Journal of Disaster Risk Science 2022年第4期13卷 521-535页

作者： Michele Nacif Antunes Susana da Silva pereira Joséluis Zêzere Adauto Emmerich Oliveira Postgraduate Program in Public Health(PPGSC) Federal University of Espírito SantoVitoriaEspírito Santo 29047-105Brazil Centre for Geographical Studies Institute of Geography and Spatial PlanningUniversidade de Lisboa1600-276 LisbonPortugal Associate Laboratory TERRA 1349-017 LisbonPortugal

Disaster communication guidelines emphasize that journalists should be aware of past major disasters and draw lessons from the coverage of those events.The press is an important source for the evolution of historical disaster and risk research paradigms over time.This study explored the top 10 damaging hydrogeomorphological events in Portugal selected from the disaster database,which includes events that caused human damages(fatalities,injured,missing,evacuated,and displaced)reported over a period of 151years(1865–2015)by the Portuguese newspaper Diário de Notícias(DN).News analysis was guided by the news protocol.The analysis of the news published in DN enabled us to identify textual marks that present interconnections in the journalistic coverage and produce discursive standards for these disasters.The textual marks were associated with the hazard and risk paradigms.The discursive standards of DN did not clearly reflect the ruptures in the hazard paradigms.As a rule,the journalistic reports contributed to the naturalization of disasters and the gap in public understanding of risks,by presenting an approach focused on relief actions—ignoring social issues,vulnerability,and population resilience—reducing the discourse of preparedness for future disasters.

关键词： Disaster journalism Hydrogeomorphological events News protocol Portugal Print media

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Behavior of wood basic density according to environmental variables

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Journal of Forestry Research 2022年第2期33卷 497-505页

作者： gabriel Marcos Vieira Oliveira JoséMárcio de Mello Carlos Rogério de Mello JoséRoberto Soares Scolforo Eder pereira Miguel Thiago Campos Monteiro Brazil Institute of Agricultural and Forestry Defense of Espírito Santo(IDAF) Av.Lourival Lugon Moulinnº300CentroJerônimo MonteiroES CEP:29.550-000Brazil Department of Forestry Sciences Universidade Federal de Lavras-UFLACaixa Postal 3037LavrasMG CEP:37.200-000Brazil Engineering Department Universidade Federal de Lavras-UFLACaixa Postal 3037LavrasMG CEP:37.200-000Brazil Forestry Engineering Department Faculdade de TecnologiaUniversity of Brasilia-UnBCampus Universitário Darcy RibeiroCaixa Postal 4357Asa Norte-BrasíliaDF CEP:70910-900Brazil Department of Forestry Engineering and Technology Universidade Federal do Paraná-UFPRAv.Pref.Lothário Meissner632Jardim BotânicoCuritibaPR CEP:80.210-170Brazil

The relationships between climate conditions and wood density in tropical forests are still poorly understood.To quantify spatial dependence of wood density in the state of Minas Gerais(MG,Brazil),map spatial distribution of density,and correlate density with climate variables,we extracted data from the Forest Inventory of Minas Gerais for 1988 trees scaled throughout the territory and measured wood density of discs removed from the trees.Environmental variables were extracted from the database of the Ecological-Economic Zoning of Minas Gerais.For spatial analysis,tree densities were measured at 44 georeferenced sampling points.The data were subjected to exploratory analysis,variography,cross-validation,model selection,and ordinary kriging.The relationships between wood density and environmental variables were calculated using dispersion matrices,linear correlation,and regression.Wood density proved to be highly spatially dependent,reaching a correlation of 96%,and was highly continuous over a distance of 228 km.The distribution of wood density followed a continuous gradient of 514-659 kg m^(−3),enabling corre-lation with environment variables.Density was correlated with mean annual precipitation(−0.57),temperature(0.63),and evapotranspiration(0.83).Geostatistical methods proved useful in predicting wood density in native tropical forests with different climate conditions.Our results confirmed the sensitivity of wood density to climate change,which could affect future carbon stock in forests.

关键词： Biomass Climate variables Geostatistics Hardwood Forest inventory Minas Gerais

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Impacts of COVID-19 on children and adolescents:A systematic review analyzing its psychiatric effects

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World Journal of Psychiatry 2022年第11期12卷 1313-1322页

作者： Italo Wanderson de Moura gabriel Danielly Gonçalves Sombra Lima Jeully pereira Pires Nélio Barreto Vieira Aloisio Antonio Gomes de Matos Brasil Yara Talita Gomes pereira Erika Galvao de Oliveira HildsonLeandro de Menezes Nadia Nara Rolim Lima Alberto Olavo Advíncula Reis Ruan Neto pereira Alves Uanderson pereira da Silva Jucier Gonçalves Junior Modesto Leite Rolim-Neto School of Medicine Faculty of Medicine of Juazeiro do Norte-FMJ/IDOMEDJuazeiro do Norte 63040-360CearaBrazil School of Medicine Federal University of CaririBarbalha 63048-080CearaBrazil Mais Médicos Program Federal Government of Brazil-Ministry of HealthIguatu 63048-080CearaBrazil Julio Alves de Lira Hospital and Maternity Hospital HALHMBelo Jardim 55157-290PernambucoBrazil Nursing Department Doctor Leão Sampaio University Center-UNILEAOJuazeiro do Norte 63.041-140CearaBrazil Julio Alves de Lira Hospital and Maternity Hospital JALHMBelo Jardim 55157-290PernambucoBrazil Graduate Program(Post-Doctoral)in Neuro-Psychiatry UFPERecife 50670-901PernambucoBrazil Postgraduate Program(Master’s and Doctorate)in Public Health University of São Paulo-USPSão Paulo 01246-904São PauloBrazil School of Education USPSão Paulo 05508-040São PauloBrazil Internal Medicine-Division of Rheumathology at Hospital das Clínicas São Paulo UniversitySão Paulo 01246-903São PauloBrazil

OBJECTIVE To summarize the most relevant data from a systematic review on the impact of COVID-19 on children and adolescents,particularly analyzing its psychiatric effects.METHODS This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses(PRISMA)guidelines and included experimental studies(randomized-individually or pooled-and non-randomized controlled trials),observational studies with a group for internal comparison(cohort studies-prospective and retrospective-and case-control)and qualitative studies in the period from 2021 to 2022.RESULTS The search identified 325 articles;we removed 125 duplicates.We selected 200 manuscripts,chosen by title and selected abstracts.We excluded 50 records after screening titles and abstracts,as they did not meet the inclusion criteria.We retrieved 150 records selected for a full reading.We excluded 90 text articles and we selected 25 records for the(n)final.Limitations:Due to the short period of data collection,from 2021 to 2022,there is a possibility of lack of relevant studies related to the mental health care of children and adolescents.In addition,there is the possibility of publication bias,such as only significant findings being published.CONCLUSION The impact of COVID-19 on the mental health of children and adolescents is of great concern to child and youth psychiatry.Situations such as fear,anxiety,panic,depression,sleep and appetite disorders,as well as impairment in social interactions caused by psychic stress,are punctual markers of pain and psychic suffering,which have increasing impacts on the mental health panorama of children and adolescents globally,particularly in vulnerable and socially at-risk populations.

关键词： Child psychiatry Adolescent psychiatry Mental health COVID-19 Kids Teens

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Genetic testing vs microforceps biopsy in pancreatic cysts:Systematic review and meta-analysis

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World Journal of Gastroenterology 2019年第26期25卷 3450-3467页

作者： Sandra Faias luisa pereira Angelo luis Paula Chaves Marilia Cravo Department of Gastroenterology Instituto Portugues de Oncologia de Lisboa de Francisco GentilEPELisboa 1099-023Portugal Faculdade de Ciencias da Seude Universidade da Beira InteriorCovilha 200-506Portugal GRUBI-Grupo de Revisoes Sistematicas Universidade da Beira InteriorCovilha 6200-506Portugal Centro de Matemática e Aplicacoes(CMA-UBI) Universidade da Beira InteriorCovilha 6200-506Portugal Centro de Investigacao em Ciencias da Saude(CICS-UBI) Universidade da Beira InteriorCovilha 6200-506Portugal Department of Pathology Instituto Portugues de Oncologia de Lisboa de Francisco GentilEPELisboa 1099-023Portugal Department of Gastroenterology Hospital Beatriz AngeloLoures 2674-514Portugal Faculdade de Medicina Universidade de LisboaLisboa 1099-023Portugal

BACKGROUND Carcinoembryonic antigen(CEA)and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic neoplasms.Genetic testing and microforceps biopsy are promising tools for pre-operative diagnostic improvement but comparative performance of both methods is unknown.AIM To compare the accuracy of genetic testing and microforceps biopsy in pancreatic cysts referred for surgery.METHODS We performed a literature search in Medline,Scopus,and Web of Science for studies evaluating genetic testing of cystic fluid and microforceps biopsy of pancreatic cysts,with endoscopic ultrasound with fine-needle aspiration(EUSFNA)prior to surgery and surgical pathology as reference standard for diagnosis.We evaluated the diagnostic accuracy for:1-benign cysts;2-mucinous low-risk cysts;3-high-risk cysts,and the diagnostic yield and rate of correctly identified cysts with microforceps biopsy and molecular analysis.We also assessed publication bias,heterogeneity,and study quality.RESULTS Eight studies,including 1206 patients,of which 203(17%)referred for surgery who met the inclusion criteria were analyzed in the systematic review,and seven studies were included in the meta-analysis.Genetic testing and microforceps biopsies were identical for diagnosis of benign cysts.Molecular analysis was superior for diagnosis of both low and high-risk mucinous cysts,with sensitivities of 0.89(95%CI:0.79-0.95)and 0.57(95%CI:0.42-0.71),specificities of 0.88(95%CI:0.75-0.95)and 0.88(95%CI:0.80-0.93)and AUC of 0.9555 and 0.92,respectively.The diagnostic yield was higher in microforceps biopsies than in genetic analysis(0.73 vs 0.54,respectively)but the rates of correctly identified cysts were identical(0.73 with 95%CI:0.62-0.82 vs 0.71 with 95%CI:0.49-0.86,respectively).CONCLUSION Genetic testing and microforceps biopsies are useful second tests,with identical results in benign pancreatic cysts.Genetic analysis performs better for low-and high-risk cysts but has lower diagnostic yield.

关键词： Pancreatic cysts Endoscopic ultrasound Endoscopic ultrasound with fineneedle aspiration Genetic testing Microforceps biopsy Molecular analysis KRAS Carcinoembryonic antigen Cytology

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