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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

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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

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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

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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

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Prognostic importance of lymph node yield after curative resection of gastroenteropancreatic neuroendocrine tumours

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World Journal of Clinical Oncology 2020年第4期11卷 205-216页

作者： Jaseela Chiramel Rose Almond Astrid Slagter Adeel Khan Xin Wang Kok Haw Jonathan Lim Melissa Frizziero Bipasha Chakrabarty Annamaria Minicozzi Angela Lamarca Wasat Mansoor richard A hubner Juan William Valle Mairéad Geraldine McNamara Department of Medical Oncology The Christie NHS Foundation TrustManchester M204BXUnited Kingdom Royal Free London NHS Foundation Trust London NW32QGUnited Kingdom Statistics Group Digital ServicesThe Christie NHS Foundation TrustManchesterM204BXUnited Kingdom Antoni van Leeuwenhoek/Netherlands Cancer Institute Amsterdam 1066 CxNetherlands Department of Pathology The Christie NHS Foundation TrustManchester M204BXUnited Kingdom Department of Surgery Barts Health NHS TrustLondon EC1A 7BEUnited Kingdom Division of Cancer Sciences University of ManchesterManchester M139PLUnited Kingdom

BACKGROUND The prognostic significance of lymph nodes(LNs)metastases and the optimum number of LN yield in gastroenteropancreatic neuroendocrine tumours(GEP NETs)undergoing curative resection is still *** studies have demonstrated that cure rate for patients with GEP NETs can be improved by the resection of the primary tumour and regional lymphadenectomy AIM To evaluate the effect of lymph node(LN)status and yield on relapse-free survival(RFS)and overall survival(OS)in patients with resected GEP *** Data on patients who underwent curative resection for GEP NETs between January 2002 and March 2017 were analysed *** 3 tumours(Ki67>20%)were *** Cox proportional hazard models were computed for RFS and OS and assessed alongside cut-point analysis to distinguish a suitable binary categorisation of total LNs retrieved associated with *** A total of 217 patients were included in the *** median age was 59 years(21-97 years)and 51%(n=111)were *** tumour sites were small bowel(42%),pancreas(25%),appendix(18%),rectum(7%),colon(3%),gastric(2%),others(2%).Median follow up times for all patients were 41 mo(95%CI:36-51)and 71 mo(95%CI:63–76)for RFS and OS respectively;50 relapses and 35 deaths were *** were retrieved in 151 *** or more LNs were harvested in 106 patients and LN positivity reported in 114 *** or more positive LNs were detected in 62 *** result of univariate analysis suggested perineural invasion(P=0.0023),LN positivity(P=0.033),LN retrieval of≥8(P=0.047)and localisation(P=0.0049)have a statistically significant association with shorter RFS,but there was no effect of LN ratio on RFS:P=0.1 or OS:P=*** necrosis(P=0.021)and perineural invasion(P=0.016)were the only two variables significantly associated with worse *** the final multivariable analysis,localisation(pancreas HR=27.33,P=0.006,small bowel HR=32.44,P=0.005),and retrieval of≥8 LNs(HR=2.7,P

关键词： Well differentiated neuroendocrine tumours Pancreatic neuroendocrine tumours Small intestinal neuroendocrine tumours Ki67 Lymph node ratio Lymph node retrieval Lymph node positivity Relapse-free survival Overall survival

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