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Hepatobiliary Surgery and Nutrition 2022年第1期11卷 147-149页

作者： mairéad g.mcnamara Division of Cancer Sciences University of Manchester&The Christie NHS Foundation TrustManchesterUK

The incidence of biliary tract cancer(BTC)(1),including gallbladder cancer(gBC)(2),is *** curative surgery is possible in only approximately 20%,and adjuvant capecitabine,versus observation after resection,has been reported to improve survival in a prespecified sensitivity and per-protocol analyses of the phase 3 randomised trial BILCAP(capecitabine compared with observation in resected BTC)(adjusting for minimisation factors,nodal status,grade,and gender)(3,4).The prognosis for patients with advanced BTC is poor;the median overall survival(OS)for patients receiving standard of care cisplatin/gemcitabine in the first-line setting was 11.7 months in the advanced Biliary Cancer-02(ABC-02)study(5).There has been no alteration in the established choice of first-line systemic treatment for advanced BTC for over a ***,a recent press release announced that the phase 3 randomised study of durvalumab in combination with cisplatin/gemcitabine versus placebo with cisplatin/gemcitabine as a first-line treatment for patients with advanced BTC(TOPAZ-1)had met its primary endpoint of OS at the interim analysis;detailed results are awaited(NCT03875235).

关键词： patients gallbladder cancer

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

The microbiome as a potential diagnostic biomarker for pancreatic ductal adenocarcinoma(PDAC)

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Hepatobiliary Surgery and Nutrition 2022年第5期11卷 752-754页

作者： Roseanna C.Wheatley Juan W.Valle mairéad g.mcnamara Division of Cancer Sciences School of Medical SciencesFaculty of Biology Medicine and HealthUniversity of ManchesterManchesterUK Department of Medical Oncology The Christie NHS Foundation TrustManchesterUK

Pancreatic ductal adenocarcinoma(PDAC)is a major cause of cancer-related death *** recent advances in treatment options,prognosis remains poor,and data estimates from the United States(US)show that PDAC will surpass colorectal cancer to become the second most common cause of cancer-related death by 2040(1).Surgery followed by adjuvant chemotherapy is the only potentially curative treatment option for patients with PDAC;however,the majority present with advanced stage,non-resectable *** diagnosis could improve the dismal prognosis for this patient group,but this remains challenging due to numerous factors including a lack of approved biomarkers and screening programmes,and non-specificity or late presentation of symptoms.

关键词： Surgery adenocarcinoma diagnosis

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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 gnificant 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

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

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

Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance

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World Journal of gastroenterology 2014年第29期20卷 9912-9921页

作者： Sinéad M Smith Colm O’Morain Deirdre mcnamara Department of Clinical Medicine Trinity College DublinTrinity CentreAdelaide and Meath Hospital School of Pharmacy and Pharmaceutical Sciences Trinity College Dublin Department of gastroenterology Adelaide and Meath Hospital

The gram-negative bacterium Helicobacter pylori(***)causes chronic gastritis,gastric and duodenal ulcers,gastric cancer and mucosa-associated lymphoid tissue *** is recommended in all symptomatic *** current treatment options for *** infection are outlined in this review in light of the recent challenges in eradication success,largely due to the rapid emergence of antibiotic resistant strains of *** resistance is a constantly evolving process and numerous studies have shown that the prevalence of *** antibiotic resistance varies significantly from country to country,and even between regions within the same *** addition,recent data has shown that previous antibiotic use is associated with harbouring antibiotic resistant *** surveillance of antibiotic resistance is warranted to guide clinicians in their choice of *** resistance is assessed by *** culture and antimicrobial susceptibility *** developed molecular tests offer an attractive alternative to culture and allow for the rapid molecular genetic identification of *** and resistance-associated mutations directly from biopsy samples or bacterial culture *** evidence indicates that surveillance of antimicrobial resistance by susceptibility testing is feasible and necessary to inform clinicians in their choice of therapy for management of *** infection.

关键词： Helicobacter pylori Antibiotic resistance Antimicrobial susceptibility testing Polymerase chain reaction Molecular test

Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection?

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World Journal of gastroenterology 2018年第9期24卷 971-981页

作者： Denise E Brennan Colin Dowd Colm O'Morain Deirdre mcnamara Sinéad M Smith Department of Clinical Medicine School of Medicine Trinity College Dublin

AIM To evaluate the association between virulence factor status and antibiotic resistance in Helicobacter pylori(H. pylori)-infected patients in Ireland. METHODS DNA was extracted from antral and corpus biopsies obtained from 165 H. pylori-infected patients. genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the genotype Helico DR assay. cag A and vac A genotypes were investigated using PCR. RESULTS Primary, secondary and overall resistance rates for clarithromycin were 50.5%(n = 53/105), 78.3%(n = 47/60) and 60.6%(n = 100/165), respectively. Primary, secondary and overall resistance rates for fluoroquinolones were 15.2%(n = 16/105) and 28.3%(n = 17/60) and 20%(n = 33/165), respectively. Resistance to both antibiotics was 12.4%(n = 13/105) in treatment-na?ve patients, 25%(n = 15/60) in those previously treated and 17%(n = 28/165) overall. A cag A-positive genotype was detected in 22.4%(n = 37/165) of patient samples. The dominant vac A genotype was S1/M2 at 44.8%(n = 74/165), followed by S2/M2 at 26.7%(n = 44/165), S1/M1 at 23.6%(n = 39/165) and S2/M1 at 4.8%(n = 8/165). Primary clarithromycin resistance was significantly lower in cag A-positive strains than in cag A-negative strains [32%(n = 8/25) vs 56.3%(n = 45/80); P = 0.03]. Similarly, in patients infected with more virulent H. pylori strains bearing the vac A s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vac A s2 genotype, [41%(n = 32/78) vs 77.8%(n = 21/27); P = 0.0001]. No statistically significant association was found between primary fluoroquinolone resistance and virulence factor *** genotypic H. pylori clarithromycin resistance is high and cag A-negative strains are dominant in our population. Less virulent(cag A-negative and vac A S2-containing) strains of H. pylori are associated with primary clarithromycin resistance.

关键词： Helicobacter pylori Antibiotic resistance Fluoroquinolone Clarithromycin Virulence factor VacA CagA

Exploring Loss and Damage at the International Climate Change Talks

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International Journal of Disaster Risk Science 2014年第3期5卷 242-246页

作者： Karen Elizabeth mcnamara School of geography Planning and Environmental ManagementThe University of QueenslandBrisbaneQLD 4072Australia

In recent years, there has been a growing need to address loss and damage as a result of climate change through international processes. At the most recent November 2013 international climate change talks in Warsaw, 194 countries negotiated the best way to establish institutional arrangements for loss and damage under the United Nations Framework Convention on Climate Change. Such a decision to establish these arrangements was made in 2012 in Doha in a decision known as the‘‘Doha gateway.’’ While the 19th(2013) Conference of the Parties succeeded in delivering the Warsaw International Mechanism for Loss and Damage Associated with Climate Change Impacts, there was concern by some negotiators earlier into the conference that this would never transpire given the staunch disagreements between countries and lobbying blocks on a way forward. This article provides a brief historical overview of loss and damage at the climate change talks, and examines the key discourses defining this issue between 2011 and 2013 by analyzing submissions by lobbying blocks and member countries, and final negotiated texts. These discourses revolve around causality and solutions, compensation, and the relationship between loss and damage and adaptation.

关键词： adaptation Climate change Loss and damage Mitigation United Nations

Molecular detection of Helicobacter pylori antibiotic resistance in stool vs biopsy samples

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World Journal of gastroenterology 2016年第41期22卷 9214-9221页

作者： Denise E Brennan Joseph Omorogbe Mary Hussey Donal Tighe grainne Holleran Colm O'Morain Sinéad M Smith Deirdre mcnamara Department of Clinical Medicine School of Medicine Trinity College Dublin School of Pharmacy and Pharmaceutical Sciences Trinity College Dublin

AIM To compare(1) demographics in urea breath test(UBT) vs endoscopy patients; and(2) the molecular detection of antibiotic resistance in stool vs biopsy *** Six hundred and sixteen adult patients undergoing endoscopy or a UBT were prospectively recruited to the study. The geno Type Helico DR assay was used to detect Helicobacter pylori(H. pylori) and antibiotic resistance using biopsy and/or stool samples from CLOpositive endoscopy patients and stool samples from UBT-positive patients. RESULTS Infection rates were significantly higher in patients referred for a UBT than endoscopy(overall rates: 33% vs 19%; treatment-na?ve patients: 33% vs 14.7%, respectively). H. pylori-infected UBT patients were younger than H. pylori-infected endoscopy patients(41.4 vs 48.4 years, respectively, P gher percentage of H. pylori-infected males in the endoscopy-compared to the UBT-cohort(52.6% vs 33.3%, P = 0.03). The geno Type Helico DR assay was more accurate at detecting H. pylori infection using biopsy samples than stool samples [98.2%(n = 54/55) vs 80.3%(n =53/66), P g stool and biopsy samples from CLO-positive endoscopy patients revealed a higher detection rate ofresistance-associated mutations using stool samples compared to biopsies. The concordance rates between stool and biopsy samples for the detection of H. pylori DNA, clarithromycin and fluoroquinolone resistance were just 85%, 53% and 35%, respectively. CONCLUSION Differences between endoscopy and UBT patients provide a rationale for non-invasive detection of H. pylori antibiotic resistance. However, the geno Type Helico DR assay is an unsuitable approach.

关键词： Helicobacter pylori Antibiotic resistance Clarithromycin Fluoroquinolone Molecular methods