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Potential utility of liquid biopsies in the management of patients with biliary tract cancers:A review

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World Journal of Gastrointestinal Oncology 2021年第9期13卷 1073-1085页

作者： Rohan Shotton Angela Lamarca juan valle Mairéad G McNamara Department of Medical Oncology The Christie NHS Foundation TrustManchester M204BXUnited Kingdom Division of Cancer Sciences School of Medical SciencesFaculty of BiologyMedicine and HealthUniversity of ManchesterManchester M139PLUnited Kingdom

Biliary tract cancer,comprising gallbladder cancer,cholangiocarcinoma and ampullary cancer,represents a more uncommon entity outside high-endemic areas,though global incidence is *** majority of patients present at a late stage,and 5-year survival remains *** stage disease is incurable,and though palliative chemotherapy has been shown to improve survival,further diagnostic and therapeutic options are required in order to improve patient *** certain subtypes of biliary tract cancer are relatively rich in targetable mutations,attaining tumour tissue for histological diagnosis and treatment monitoring is challenging due to locoregional anatomical constraints and patient *** biopsies offer a safe and convenient alternative to invasive procedures and have great potential as diagnostic,predictive and prognostic *** this review,the current standard of care for patients with biliary tract cancer,future treatment horizons and the possible utility of liquid biopsies within a variety of contexts will be *** tumour DNA,circulating microRNA and circulating tumour cells are discussed with an overview of their potential applications in management of biliary tract cancer.A summary is also provided of currently recruiting clinical trials incorporating liquid biopsies within biliary tract cancer research.

关键词： Biliary tract cancer Liquid biopsy Circulating tumour DNA Cell free DNA Circulating tumour cells Biomarkers

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World Journal of Gastroenterology 2018年第6期24卷 671-679页

作者： Alexandra R Lewis Xin Wang Laurice Magdalani Paolo D'Arienzo Colsom Bashir Was Mansoor Richard Hubner juan W valle Mairéad G McNamara Department of Medical Oncology The Christie NHS Foundation Trust Department of Biostatistics The Christie NHS Foundation Trust Division of Medical Sciences Scuola Superiore Sant’Anna Department of Clinical Psychology The Christie NHS Foundation Trust Division of Cancer Sciences University of Manchester

AIM To compare health-related quality of life(HRQoL),anxiety, depression, and impulsivity scores in patients with and without carcinoid syndrome(CS), and correlated them with serum 5-hydroxyindoleacetic acid(5-HIAA) *** Patients with advanced gastroenteropancreatic neuroendocrine tumours(GEPNET), with and without CS completed HRQoL QLQ-C30 and ***21, Hospital Anxiety and Depression Scale(HADS) and Barratt Impulsivity Scale(BIS) questionnaires. Twosample Wilcoxon test was applied to assess differences in serum 5-HIAA levels, two-sample Mann-Whitney U test for HRQoL and BIS, and proportion test for HADS, between those with and without *** Fifty patients were included; 25 each with and without CS. Median 5-HIAA in patients with and without CS was 367 nmol/L and 86 nmol/L, respectively(P = 0.003). Scores related to endocrine symptoms were significantly higher amongst patients with CS(P = 0.04) and scores for disease-related worries approached significance in the group without CS, but no other statistically-significant differences were reported between patients with and without CS in responses on QLQ-C30 or ***21. Fifteen patients(26%) scored ≥ 8/21 on anxiety scale, and 6(12%) scored ≥ 8/21 on depression scale. There was no difference in median 5-HIAA between those scoring < or ≥ 8/21 on anxiety scale(P = 0.53). There were no statistically significant differences between groups in first or second-order factors(BIS) or total sum(P = 0.23).CONCLUSION Excepting endocrine symptoms, there were no significant differences in HRQoL, anxiety, depression or impulsivity between patients with advanced GEPNET, with or without CS. Over one quarter of patients had high anxiety scores, unrelated to peripheral serotonin metabolism.

关键词： Gastroenteropancreatic neuroendocrine tumours Carcinoid syndrome Quality of life Anxiety Depression Impulsivity

Measuring frailty in patients with severe aortic stenosis:a comparison of the edmonton frail scale with modified fried frailty assessment in patients undergoing transcatheter aortic valve replacement

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Journal of Geriatric Cardiology 2020年第7期17卷 441-446页

作者： Francisco J Romeo Maximiliano Smietniansky Mariela Cal Cristian Garmendia juan M valle Raleigh Ignacio MSeropian Mariano Falconi Pablo Oberti Vadim Kotowicz Carla RAgatiello Daniel H Berroca Division of Interventional Cardiology Hospital Italiano de Buenos AiresBuenos AiresArgentina Division of Internal Medicine and Geriatrics Hospital Italiano de Buenos AiresBuenos AiresArgentina Division Cardiology Hospital Italiano de Buenos AiresBuenos AiresArgentina Division of Cardiovascular Surgery Hospital Italiano de Buenos AiresBuenos AiresArgentina

Frailty is generally defined as a clinical syndrome of decreased physiologic reserve which drives to increased vulnerability and susceptibility to different stressors together with poor recovery to homeostasis.[1]The relevance of frailty status in a wide range of prospective cohorts is mostly related to an increasing burden in both mortality,hospital readmissions,disability,and falls.

关键词： Aortic stenosis Frailty Transcatheter aortic valve replacement

Identification of patients with pancreatic adenocarcinoma due to inheritable mutation:Challenges of daily clinical practice

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World Journal of Gastrointestinal Oncology 2019年第2期11卷 102-116页

作者： Alexander JP Fulton Angela Lamarca Christina Nuttall Lynne McCallum Rille Pihlak Derek O'Reilly Fiona Lalloo Mairéad G McNamara Richard A Hubner Tara Clancy juan W valle Department of Medical Oncology The Christie NHS Foundation Trust Hepato-pancreato-biliary Surgical Department Manchester Royal InfirmaryCentral Manchester University Hospitals NHS Foundation Trust Manchester Centre for Genomic Medicine Central Manchester University Hospitals NHS Foundation Trust Saint Mary's Hospital

BACKGROUND Identification of germ-line mutations in pancreatic ductal adenocarcinoma(PDAC) could impact on patient/*** To assess the referral pathways for genetic consultations in *** Electronic records of PDAC patients were reviewed retrospectively. Patients eligible for genetic consultation referral were identified following the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer(EUROPAC)*** Four-hundred patients were eligible. Of 113 patients(28.3%) meeting EUROPAC criteria, 8.8% were referred for genetic opinion. Germ-line mutations were identified in 0.75% of the whole *** referrals and increased awareness may be able to overcome the low rate of successful genetic appointments.

关键词： Genetic counselling Pancreatic adenocarcinoma Genetic consultation BRCA Germline

Pancreatic cancer: Are 'liquid biopsies' ready for prime-time?

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World Journal of Gastroenterology 2016年第32期22卷 7175-7185页

作者： Alexandra R Lewis juan W valle Mairead G Mc Namara The Christie NHS Foundation Trust M20 4BX ManchesterUnited Kingdom Institute of Cancer Sciences University of ManchesterM20 4BX ManchesterUnited Kingdom

Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells(CTCs) have been investigated as a potential "liquid biopsy" in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms. Circulating tumour DNA(ct DNA) has also been detected in pancreas cancer with a sensitivity ranging from 26%-100% in studies across different platforms and using different genetic markers. However, there is no clear consensus on which platform is the most effective for detection, nor which genetic markers are the most useful to use. Potential roles of liquid biopsies include diagnosis, screening, guiding therapies and prognosis. The presence of CTCs or ct DNA has been shown to be of prognostic value both at diagnosis and after treatment in patients with pancreatic cancer. However, more prospective studies are required before this promising technology is ready for adoption into routine clinical practice.

关键词： Pancreatic Cancer Liquid biopsy Circulating Tumour Cells Circulating Tumour DNA

Failure to Rescue as a Quality Metric in Congenital Heart Surgeries in a High-Complexity Service Provider Institution Located in a Middle-Income Country

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Congenital Heart Disease 2024年第2期19卷 207-218页

作者： Gustavo Cruz Santiago Pedroza juan F.Vélez Jessica Largo juan F.Tejada Jorge H.Mejía-Mantilla Departamento de Anestesiología Fundación Valle del LiliCali760032Colombia Centro de Investigaciones Clínicas Fundación Valle del LiliCali760032Colombia Departamento de Cardiología Pediátrica Fundación Valle del LiliCali760032Colombia Facultad de Medicina Universidad IcesiCali760031Colombia Unidad de Cuidado Intensivo Fundación Valle del LiliCali760032Colombia

Background:Failure to rescue has been an effective quality metric in congenital heart ***,mor-bidity and mortality depend greatly on non-modifiable individual factors and have a weak correlation with better-quality *** aim to measure the complications,mortality,and risk factors in pediatric patients undergoing congenital heart surgery in a high-complexity institution located in a middle-income country and compare it with other institutions that have conducted a similar ***:A retrospective observational study was conducted in a high-complexity service provider institution,in Cali,*** pediatric patients undergoing any congenital heart surgery between 2019 and 2022 were *** main outcomes evaluated in the study were complication,mortality,and failure to rescue *** and multivariate logistic regression analysis was performed with mortality as the outcome ***:We evaluated 308 congenital heart *** the outcomes,201(65%)complications occurred,23(7.5%)patients died,and the FTR of the entire cohort was 11.4%.The presence of a postoperative complication(OR 14.88,CI 3.06–268.37,p=0.009),age(OR 0.79,CI 0.57–0.96,p=0.068),and urgent/emergent surgery(OR 8.14,CI 2.97–28.66,p<0.001)were the most significant variables in predicting ***:Failure to rescue is an effective and comparable quality measure in healthcare institutions and is the major contributor to postoperative mortality in congenital heart *** our higher mortality and complication rate,we obtained a comparable failure to rescue rate to high-income countries’health institutions.

关键词： Congenital heart surgery complication mortality failure to rescue quality metric

Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy

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World Journal of Gastroenterology 2016年第26期22卷 6065-6075页

作者： Angela Lamarca Christina Rigby Mairéad G Mc Namara Richard A Hubner juan W valle Department of Medical Oncology The Christie NHS Foundation Trust Institute of Cancer Sciences University of Manchester Manchester Academic Health Science Centre

AIM: To determine the impact(morbidity/mortality) of biliary stent-related events(SRE)(cholangitis or stent obstruction) in chemotherapy-treated pancreaticobiliary ***: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records(Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE(defined as time from first stenting before chemotherapy to date of SRE). Progressionfree survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression(univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing ***: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent(the remainder were plastic). The median time of follow-up was 9.6 mo(range 2.2 to 26.4). Forty-one patients(43%)developed a SRE during follow-up [cholangitis(39%), stent obstruction(29%), both(32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none(37%), chemotherapy delay(24%), discontinuation(17%) and death(22%). The median time-to-SRE was 4.4 mo(95%CI: 3.6-5.5). Patients with severe comorbidities(P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3(95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival(P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE(SRE group vs no-SRE group).CONCLUSION: SREs are common and impact on patient's morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs.

关键词： Advanced biliary tract cancer Pancreatic cancer Biliary obstruction Biliary stent Stent-related even

Retrospective study on mixed neuroendocrine non-neuroendocrine neoplasms from five European centres

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World Journal of Gastroenterology 2019年第39期25卷 5991-6005页

作者： Melissa Frizziero Xin Wang Bipasha Chakrabarty Alexa Childs Tu V Luong Thomas Walter Mohid S Khan Meleri Morgan Adam Christian Mona Elshafie Tahir Shah Annamaria Minicozzi Wasat Mansoor Tim Meyer Angela Lamarca Richard A Hubner juan W valle Mairéad G McNamara Department of Medical Oncology The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Department of Analytics and Development The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Department of Pathology The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Department of Medical Oncology Royal Free London NHS Foundation TrustLondon NW3 2QGUnited Kingdom UCL Cancer Institute University College LondonLondon WC1E 6AGUnited Kingdom Department of Histopathology Royal Free London NHS Foundation TrustLondon NW3 2QGUnited Kingdom Department of Gastroenterology and Medical Oncology Edouard Herriot HospitalHospices Civils de LyonLyon 69003France Department of Gastroenterology Cardiff and Vale University Health BoardUniversity Hospital of WalesCardiff CF14 4XWUnited Kingdom Department of Cellular Pathology Cardiff and Vale University Health BoardUniversity Hospital of WalesCardiff CF14 4XWUnited Kingdom Department of Pathology University Hospitals Birmingham NHS Foundation TrustBirmingham B15 2THUnited Kingdom Department of Hepatology University Hospitals Birmingham NHS Foundation TrustBirmingham B15 2THUnited Kingdom Department of Surgical Oncology The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Division of Cancer Sciences University of ManchesterManchester M13 9PLUnited Kingdom

BACKGROUND Mixed neuroendocrine non-neuroendocrine neoplasm(MiNEN)is a rare diagnosis,mainly encountered in the gastro-entero-pancreatic *** is limited knowledge of its epidemiology,prognosis and biology,and the best management for affected patients is still to be *** To investigate clinical-pathological characteristics,treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of *** Consecutive patients with a histologically proven diagnosis of MiNEN were identified at 5 European *** data were retrospectively collected from medical *** samples were reviewed to ascertain compliance with the 2017 World Health Organisation definition of *** responses to systemic treatment were assessed according to the Response Evaluation Criteria in Solid Tumours ***-Meier analysis was applied to estimate survival *** between clinical-pathological characteristics and survival outcomes were explored using Log-rank test for equality of survivors functions(univariate)and Cox-regression analysis(multivariable).RESULTS Sixty-nine consecutive patients identified;Median age at diagnosis:64 ***:63.8%.Localised disease(curable):53.6%.Commonest sites of origin:colon-rectum(43.5%)and oesophagus/oesophagogastric junction(15.9%).The neuroendocrine component was;predominant in 58.6%,poorly differentiated in 86.3%,and large cell in 81.25%,of cases *** distant metastases analysed(73.4%)were occupied only by a poorly differentiated neuroendocrine ***-four percent of patients with localised disease underwent curative surgery;53%also received perioperative treatment,most often in line with protocols for adenocarcinomas from the same sites of *** was offered to most patients(68.1%)with advanced disease,and followed protocols for pure neuroendocrine carcinomas or adenocarcinomas in equal *** localised cases,median recurre

关键词： Mixed neuroendocrine non-neuroendocrine neoplasm 2017 World Health Organisation classification Mixed adeno-neuroendocrine carcinoma Gastro-enteropancreatic tract Digestive system Neuroendocrine neoplasms Survival outcomes

The potential of starch-chitosan blends with poloxamer for the preparation of microparticles by spray-drying

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Particuology 2024年第6期89卷 1-10页

作者： juan Enrique Barranco-García Carolina Caicedo Enrique Javier Jiménez-Regalado Carlos Espinoza-González Graciela Morales Rocio Yaneli Aguirre-Loredo Abril Fonseca-García Tecnológico Nacional de México/Instituto Tecnológico de Oaxaca Departamento de Química y BioquímicaAvenida Ing.Víctor Bravo Ahuja No.125Esquina Calzada Tecnológico68030OaxacaMexico Faculty of Engineering Unidad Central del Valle del Cauca(UCEVA)Carrera 17a 48-144763022TuluáColombia Centro de Investigación en Química Aplicada(CIQA) Blvd.Enrique Reyna Hermosillo 14025294SaltilloCoahuilaMexico Investigadoras por México CONAHCYT-CIQA Av.Insurgentes Sur 1562Col.Crédito Constructor03940Alcaldía Benito JuárezCDMXMexico

Using biopolymers as wall materials in spray drying poses challenges,particularly in attaining flowability and thermal stability among their physicochemical *** paper addresses these challenges by preparing microparticles using a blend of starch–chitosan and a poloxamer,commercially named Pluronic®*** aimed to elucidate the effects of varying poloxamer concentrations on the resulting particles through the spray drying *** with a poloxamer concentration of 3%(w/v)demonstrated a notably higher yield,especially when compared to those with 0%and 1%*** with 3%and 5%(w/v)poloxamer displayed a narrower particle size distribution,with the 3%blend showing a superior yield attributed to arrangements of blend components that improve flowability.X-ray diffraction analysis showcased the characteristic peaks of A-type starch form,with shifts suggesting enhanced interactions between *** with increased poloxamer content showed elevated thermal degradation temperatures,with the 3%blend registering a significant rise,opening avenues for encapsulating heat-sensitive *** study primarily focuses on the preparation and basic characterization of *** underscores the potential of blends with optimal poloxamer concentrations in microencapsulation,emphasizing further research to harness their capabilities thoroughly.

关键词： Biopolymer Starch Chitosan Pluronic®F127 Microparticles Spray drying