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Small bowel neuroendocrine tumors： From pathophysiologyto clinical approach

World Journal of Gastrointestinal Pathophysiology 2016年第1期7卷 117-124页

作者： sofia xavier Bruno Rosa JoséCotter Department of Gastroenterology Centro Hospitalar do Alto Ave4835-044 GuimarãesPortugal ICVS/3B’s Associate Laboratory University of MinhoCampus de Gualtar4710-057 BragaPortugal Life and Health Sciences Research Institute School of Health SciencesUniversity of MinhoCampus de Gualtar4710-057 BragaPortugal

Neuroendocrine tumors(NETs), defined as epithelial tumors with predominant neuroendocrine differentiation, are among the most frequent types of small bowel neoplasm. They represent a rare, slow-growing neoplasm with some characteristics common to all forms and others attributable to the organ of origin. The diagnosis of this subgroup of neoplasia is not usually straight-forward for several reasons. Being a rare form of neoplasm they are frequently not readily considered in the differential diagnosis. Also, clinical manifestations are nonspecific lending the clinician no clue that points directly to this entity. However, the annual incidence of NETs has risen in the last years to 40 to 50 cases per million probably not due to a real increase in incidence but rather due to better diagnostic tools that have become progressively available. Being a rare malignancy, investigation regarding its pathophysiology and efforts toward better understanding and classification of these tumors has been limited until recently. Clinical societies dedicated to this matter are emerging(NANETS, ENETS and UKINETS) and several guidelines were published in an effort to standardize the nomenclature, grading and staging systems as well as diagnosis and management of NETs. Also, some investigation on the genetic behavior of small bowel NETs has been recently released, shedding some light on the pathophysiology of these tumors, and pointing some new directions on the possible treating options. In this review we focus on the current status of the overall knowledge about small bowel NETs, focusing on recent breakthroughs and its potential application on clinical practice.

关键词： Neuroendocrine tumors Gastrointestinaltumors Small bowel neoplasms Carcinoid Diagnosticmarkers

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Alpha-1 antitrypsin deficiency and Pi^(*)Z allele as important co-factors in the development of liver fibrosis

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World Journal of Hepatology 2024年第8期16卷 1099-1110页

作者： Ana Isabel Ferreira Catarina Guimarães Vitor Macedo Silva sofia xavier Joana Magalhães JoséCotter Department of Gastroenterology Hospital da Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal Life and Health Sciences Research Institute School of MedicineUniversity of MinhoBraga 4710-057Portugal Life and Health Sciences Research Institute/3B’s PT Government Associate LaboratoryBraga 4710-057Portugal Department of Pulmonology Hospital Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant *** To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver *** Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology *** Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi**** age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/*** created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

关键词： Alpha-1 antitrypsin deficiency Liver fibrosis Nonalcoholic fatty liver disease fibrosis score Fibrosis-4 index Liver stiffness measurement

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Endoscopic ultrasonography-emerging applications in hepatology

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World Journal of Gastrointestinal Endoscopy 2017年第8期9卷 378-388页

作者： Joana Magalhaes Sara Monteiro sofia xavier Sílvia Leite Francisca Dias de Castro JoséCotter Gastroenterology Department Hospital Senhora da Oliveira School of Medicine University of Minho Life and Health Sciences Research Institute/3B’s PT Government Associate Laboratory

The inspection of the liver is a valuable part of the upper endoscopic ultrasonography(EUS) studies,regardless of the primary indication for the *** detailed images of the liver segments provided by EUS allows the use of this technique in the study of parenchymal liver disease and even in the diagnosis and classification of focal liver *** has also emerged as an important tool in understanding the complex collateral circulation in patients with portal hypertension and their clinical and prognostic ***,EUS-guided portal vein catheterization has been performed for direct portal pressure measurement as an alternative method to evaluate portal *** this review,the authors summarize the available evidence regarding the application of EUS to patients with liver diseases and how we can apply it in our current clinical practice.

关键词： Endoscopic ultrasonography Portal hypertension Gastroesophageal varices Focal liver lesions Liver biopsy

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Islet amyloid polypeptide & amyloid beta peptide roles in Alzheimer’s disease:two triggers, one disease

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Neural Regeneration Research 2021年第6期16卷 1127-1130页

作者： sofia Ferreira Ana F.Raimundo Regina Menezes Ivo C.Martins iBET-Instituto de Biologia Experimental e Tecnológica OeirasPortugal CEDOC-Chronic Diseases Research Center Faculdade de Ciências MédicasUniversidade Nova de LisboaLisboaPortugal ITQB-NOVA Instituto de Tecnologia Química e Biológica António XavierUniversidade Nova de LisboaOeirasPortugal Instituto de Medicina Molecular Faculdade de MedicinaUniversidade de LisboaLisbonPortugal

Alzheimer’s disease(AD)is a neurodegenerative disorder that affects millions *** to population ageing,the incidence of AD is *** patients develop cognitive decline and dementia,features for which is known,requiring permanent *** poses a major socio-economic burden on healthcare systems as AD patients’relatives and healthcare workers are forced to cope with rising numbers of affected *** recent advances,AD pathological mechanisms are not fully ***,it is clear that the amyloid beta(Aβ)peptide,which forms amyloid plaques in AD patients’brains,plays a key *** 2 diabetes,the most common form of diabetes,affects hundreds of million people *** amyloid polypeptide(IAPP)is a hormone coproduced and secreted with insulin in pancreatic β-cells,with a key role in diabetes,as it helps regulate glucose levels and control adiposity and *** to Aβ,IAPP is very amyloidogenic,generating intracellular amyloid deposits that causeβ-cell dysfunction and *** is now clear that IAPP can also have a pathological role in AD,decreasing cognitive *** harms the blood-brain barrier,directly interacts and co-deposits with Aβ,promoting diabetes-associated *** can cause a metabolic dysfunction in the brain,leading to other diabetes-related forms of ***,here we discuss IAPP association with diabetes,Aβand dementia,in the context of what we designate a“diabetes brain phenotype”AD *** approach helps to set a conceptual framework for future IAPP-based drugs against AD.

关键词： aggregation Alzheimer amylin amyloid diabetes islet amyloid polypeptide

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Neutrophile-to-lymphocyte,lymphocyte-to-monocyte,and platelet-tolymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer

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World Journal of Gastrointestinal Oncology 2022年第7期14卷 1307-1323页

作者： Tiago Cruz Tomás Ines Eiriz Marina Vitorino Rodrigo Vicente Joao Gramaca Alicia Guadalupe Oliveira Paulo Luz Mafalda Baleiras Ana sofia Spencer Luísa Leal Costa Patrícia Liu Joana Mendonca Magno Dinis Teresa Padrao Marisol Correia Goncalo Atalaia Michelle Silva Teresa Fiúza Department of Medical Oncology Hospital Professor Doutor Fernando Fonseca EPEAmadora 2720-276Portugal Department of Medical Oncology Centro Hospitalar Barreiro-Montijo EPEBarreiro 2830-003Portugal Department of Medical Oncology Hospital do Espírito Santo deÉvora EPEÉvora 7000-811Portugal Department of Medical Oncology Centro Hospitalar Universitário do Algarve EPEAlgarve 8000-386Portugal Department of Medical Oncology Hospital São Francisco XavierCentro Hospitalar Lisboa Ocidental EPELisboa 1449-005Portugal Department of Medical Oncology Hospital Santo António dos CapuchosCentro Hospital Lisboa Central EPELisboa 1169-050Portugal Department of Medical Oncology Hospital BeatrizÂngeloLoures 2674-514Portugal Department of Medical Oncology Centro Hospitalar de Trás-os-Montes e Alto Douro EPEVila Real 5000-508Portugal Department of Medical Oncology Hospital da Senhora da Oliveira EPEGuimarães 4835-044Portugal Department of Medical Oncology Hospital Garcia de Orta EPEAlmada 2805-267Portugal Department of Medical Oncology Hospital da LuzLisboa 1500-650Portugal Department of Medical Oncology Hospital Distrital de Santarém EPESantarém 2005-177Portugal

BACKGROUND Perioperative fluorouracil plus leucovorin,oxaliplatin,and docetaxel(FLOT)improves prognosis in locally advanced gastric cancer(LAGC).Neutrophil-to-lymphocyte(NLR),lymphocyte-tomonocyte(LMR),and platelet-to-lymphocyte(PLR)ratios are prognostic biomarkers but not predictive *** To assess blood ratios’(NLR,LMR and PLR)potential predictive response to FLOT and survival outcomes in resectable LAGC *** This was a multicentric retrospective study investigating the clinical potential of NLR,LMR,and PLR in resectable LAGC patients,treated with at least one preoperative FLOT cycle,from 12 Portuguese *** were compared through non-parametric Mann-Whitney *** operating characteristic curve analysis defined the cut-off values as:High PLR>141 for progression and>144 for mortality;high LMR>3.56 for T stage regression(TSR).Poisson and Cox regression models the calculated relative risks/hazard ratios,using NLR,pathologic complete response,TSR,and tumor regression grade(TRG)as independent variables,and overall survival(OS)as the dependent *** This study included 295 patients(mean age,63.7 years;59.7% males).NLR was correlated with survival time(r=0.143,P=0.014).PLR was associated with systemic progression during FLOT(P=0.022)and mortality(P=0.013),with high PLR patients having a 2.2-times higher risk of progression[95% confidence interval(CI):0.89-5.26]and 1.5-times higher risk of mortality(95%CI:0.92-2.55).LMR was associated with TSR,and high LMR patients had a 1.4-times higher risk of achieving TSR(95%CI:1.01-1.99).OS benefit was found with TSR(P=0.015)and partial/complete TRG(P<0.001).Patients without TSR and with no evidence of pathological response had 2.1-times(95%CI:1.14-3.96)and 2.8-times(95%CI:1.6-5)higher risk of *** Higher NLR is correlated with longer survival *** LMR patients have a higher risk of decreasing T stage,whereas high PLR patients have higher odds of progressing under FLOT a

关键词： Gastric cancer Perioperative fluorouracil plus leucovorin,oxaliplatin,and docetaxel Neutrophil-to-lymphocyte Lymphocyte-to-monocyte Platelet-to-lymphocyte Tumor regression grade

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Aplastic anemia and severe pancytopenia during treatment with peg-interferon,ribavirin and telaprevir for chronic hepatitis C

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World Journal of Gastroenterology 2015年第17期21卷 5421-5426页

作者： Sabela Lens Jose L Calleja Ana Campillo Jose A Carrion Teresa Broquetas Christie Perello Juan de la Revilla Zoe Marino Maria-Carlota Londono Jose M Sanchez-Tapias Alvaro Urbano-Ispizua xavier Forns Liver Unit Hospital ClinicIDIBAPSCIBERehd08036 BarcelonaSpain Liver Unit Hospital Puerta del HierroIDIPHIMCIBERehd28222 MajadahondaMadridSpain Gastroenterology Department Hospital Reina Sofia31500 TudelaNavarraSpain Liver Unit Hospital Del MarIMIMCIBERehd08003 BarcelonaSpain Hematology Unit Hospital Clinic08036 BarcelonaSpain

Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and *** due to myelotoxicity caused by these drugs may occur,but severe hematological abnormalities or aplastic anemia(AA) have not been *** collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in *** 142 cirrhotic patients receiving treatment,7 cases of severe pancytopenia(5%) were identified and three were consistent with the diagnosis of *** age was 59 years,five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver *** pancytopenia was diagnosed a median of 10 wk after the initiation of *** patients had pre-treatment hematological abnormalities related to *** six patients,antiviral treatment was interrupted at the onset of hematological *** patients died due to septic complications and one patient due to acute alveolar *** remaining patients *** pancytopenia and especially AA,are not rare during triple therapy with telaprevir in patients with advanced liver *** monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.

关键词： Aplastic anemia Hepatitis C Telaprevir Interferon Protease inhibitors

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地理编码方法对长期城市空气污染暴露与肺功能之间关联的影响

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环境与职业医学 2013年第12期30卷 969-969页

作者： Bénédicte Jacquemin Johanna Lepeule Anne Boudier Caroline Arnould Meriem Benmerad Claire Chappaz Joane Ferran Francine Kauffmann xavier Morelli Isabelle Pin Christophe Pison Isabelle Rios sofia Temam Nino Künzli Rémy Slama Valérie Siroux

[背景]地址地理编码中的错误可能会影响空气污染对健康影响的估计。[目的]研究4种地理编码技术对采用小尺度(10m×10m)分散模型估计的城市空气污染与成人肺功能之间关联的影响。[方法]测量法国格勒诺布尔市354名成年居民的1秒用力呼气容... 详细信息

[背景]地址地理编码中的错误可能会影响空气污染对健康影响的估计。[目的]研究4种地理编码技术对采用小尺度(10m×10m)分散模型估计的城市空气污染与成人肺功能之间关联的影响。[方法]测量法国格勒诺布尔市354名成年居民的1秒用力呼气容积(FEV1)与用力肺活量(FVC)。这些居民参加了两个特征明确的研究:遗传和环境对哮喘影响的流行病学研究(EGEA)和欧洲共同体呼吸系统健康调查(ECRHS)。使用单个建筑物匹配作为参考方法以及三种空间插值方法编码家庭地址。使用扩散模型估计在进行肺功能测量前的12个月期间,每个参加者住址的PM10和二氧化氮的平均浓度。以个体混杂因素及同日空气污染物暴露校正暴露与肺功能参数之间的关联。对地理编码技术在地理坐标之间距离、暴露估值以及暴露估值与健康影响之间关联等方面进行比较。[结果]利用建筑物匹配和三种插值技术估计坐标之间的中位数距离分别为26.4、27.9、35.6m。相对于基于建筑匹配的暴露估值,基于三种插值技术的PM10浓度往往被高估。当使用建筑物匹配估计暴露估值时,PM10每增加一个四分位数间距(3.0μg/m3),FVC%预测值下降3.72点(95%CI:-0.56～-6.88)、FEV1%预测值下降3.86点(95%CI:-0.14～-3.24)。当使用其他地理编码方法时,关联的幅度下降[例如,使用NavTEQ预测FVC%-2.81(95%CI:-0.26,-5.35),或者使用谷歌地图预测FVC%-2.08(95%CI:-4.63～0.47,P=0.11)。[结论]研究结果表明,当使用小尺度暴露模型估算空气污染暴露时,地理编码技术的选择可能会对健康影响的评估产生影响。

关键词：空气污染物肺功能参数编码方法地理城市健康影响编码技术用力呼气容积

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