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Impact of tumour histological subtype on chemotherapy outcome in advanced oesophageal cancer

World Journal of Gastrointestinal Oncology 2017年第8期9卷 333-340页

作者： Michael Davidson Ian Chau David Cunningham Komel Khabra Timothy Iveson Tamas Hickish Matthew Seymour Naureen Starling Royal Marsden hospital nhs foundation trust London and Surrey Southampton university hospital nhs trust and Salisbury hospital nhs foundation trust Department of Haematology and Oncology Bournemouth University and Poole Hospital NHS Trust St james’s Institute of Oncology St James’s Hospital

To investigate the impact of histology on outcome in advanced oesophageal cancer treated with first-line fluoropyrimidine-based chemotherapy. METHODSIndividual patient data were pooled from three randomised phase III trials of fluoropyrimidine-based chemotherapy ± platinum/anthracycline in patients with advanced, untreated gastroesophageal adenocarcinoma or squamous cell carcinoma (SCC) randomised between 1994 and 2005. The primary endpoint was overall survival of oesophageal cancer patients according to histology. Secondary endpoints were response rates and a toxicity composite endpoint. RESULTSOf the total 1836 randomised patients, 973 patients (53%) were eligible (707 patients with gastric cancer were excluded), 841 (86%) had adenocarcinoma and 132 (14%) had SCC. There was no significant difference in survival between patients with adenocarcinoma and SCC, with median overall survivals of 9.5 mo vs 7.6 mo (HR = 0.85, 95%CI: 0.70-1.03, P = 0.09) and one-year survivals of 38.8% vs 28.2% respectively. The overall response rate to chemotherapy was 44% for adenocarcinoma vs 33% for SCC (P = 0.01). There was no difference in the frequency of the toxicity composite endpoint between the two groups. CONCLUSIONThere was no significant difference in survival between adenocarcinoma and SCC in patients with advanced oesophageal cancer treated with fluoropyrimidine-based chemotherapy despite a trend for worse survival and less chemo-sensitivity in SCC. Tolerance to treatment was similar in both groups. This analysis highlights the unmet need for SCC-specific studies in advanced oesophageal cancer and will aid in the design of future trials of targeted agents.

关键词： Oesophageal cancer Adenocarcinoma Chemotherapy Squamous Pooled analysis

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Prognostic factors and survival after surgical resection of pancreatic neuroendocrine tumor with validation of established and modified staging systems

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Hepatobiliary & Pancreatic Diseases International 2018年第2期17卷 169-175页

作者： Nikolaos Benetatos james Hodson Ravi Marudanayagam Robert P Sutcliffe John R Isaac John Ayuk Tahir Shah Keith J Roberts The HPB Unit Queen Elizabeth Hospital Birmingham University Hospitals Birmingham NHS Foundation Trust Institute of Translational Medicine Queen Elizabeth Hospital Birmingham University Hospitals Birmingham Endocrinology Queen Elizabeth Hospital Birmingham University Hospitals Birmingham Liver Unit Queen Elizabeth Hospital Birmingham University Hospital of Birmingham NHS Foundation Trust

Background: Pancreatic neuroendocrine tumors(PNETs) display wide heterogeneity with highly variable prognosis. This study aimed to identify variables related to survival after surgical resection of ***: A total of 143 patients were identified from a prospectively maintained database. Patient characteristics were analyzed and prognostic factors for overall survival and progression-free survival were evaluated. The WHO, ENETS and AJCC scoring systems were applied to the cohort, and their ability to predict patient outcomes were ***: Multivariate analysis found that female gender, lymph node metastases and increasing WHO2010 grade to be independently associated with reduced overall survival(P < 0.05). Patients requiring multi-visceral resection or debulking surgery found to be associated with shortest survival. ROC analysis found the ENETS and AJCC scoring systems to be similarly predictive of 5-year overall survival. Modified Ki67 significantly improved its accuracy in predicting 5-year overall survival(AUROC: 0.699 vs 0.605;P < 0.01).Conclusions: Multi-visceral or debulking surgery is associated with poor outcomes. There seems to be no significant difference between enucleation and anatomical segmental resection. Available scoring systems have reasonable accuracy in stratifying disease severity, with no system identified as being *** stratification with modified grading systems needs further validation before applied in clinical practice.

关键词： Pancreatic neuroendocrine tumors Prognostic factors Validation of staging systems

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Conduit necrosis following esophagectomy: An up-to-date literature review

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World Journal of Gastrointestinal Surgery 2019年第3期11卷 155-168页

作者： Antonios Athanasiou Mairead Hennessy Eleftherios Spartalis Benjamin H L Tan Ewen A Griffiths Department of Upper GI Bariatric and Minimally Invasive Surgery St.James' University Hospital Leeds Teaching Hospitals NHS Trust Department of Anaesthesia University Hospital of Waterford Laboratory of Experimental Surgery and Surgical Research University of Athens Medical School Department of Upper Gastrointestinal Surgery University Hospitals Birmingham NHS Foundation Trust

Esophageal conduit ischaemia and necrosis is an uncommon but devastating complication of esophagectomy and remains one of the most challenging issues in surgical practice. The incidence, time interval to develop symptoms, and clinical presentation are highly variable with no predictable pattern. Evidence comes from case reports and case series rather than randomized controlled *** describe the issues surrounding conduit necrosis affecting the stomach,jejunum and colon as an esophageal replacement and the advantages,disadvantages and challenges of each type of reconstruction. Diagnosis is challenging for the most experienced surgeon. Upper gastrointestinal endoscopy and computed tomography thorax with both oral and intravenous contrast is the gold standard. Management, either conservative or interventional is also a difficult decision. Management options include conservative treatment and more aggressive treatments such as stent insertion, surgical debridement and repair of the esophagus using jejunum, colon or a musculocutaneous flap. In spite of recent advances in surgical techniques, there is no reliable strategy to manage esophageal conduit necrosis. Our review covers the pathophysiology and clinical significance of esophageal necrosis while highlighting current techniques of prevention, diagnosis and treatment of this life-threatening condition.

关键词： Esophagectomy Esophageal cancers Esophagogastric anastomosis

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Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus

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World Journal of Gastroenterology 2013年第48期19卷 9282-9293页

作者： Fergus Noble Luke Nolan Adrian C Bateman james P Byrne Jamie J Kelly Ian S Bailey Donna M Sharland Charlotte N Rees Timothy J Iveson Tim J Underwood Andrew R Bateman Cancer Sciences Unit Faculty of Medicine University of Southampton Southampton SO16 6YD United Kingdom Department of Surgery University Hospital Southampton NHS Foundation Trust Southampton SO16 6YD United Kingdom Department of Cellular Pathology University Hospital Southampton NHS Foundation Trust Southampton SO16 6YD United Kingdom Cancer Care University Hospital Southampton NHS Foundation Trust Southampton SO16 6YD United Kingdom

AIM:To assess tumour regression grade(TRG)and lymph node downstaging to help define patients who benefit from neoadjuvant ***:Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005and 2011 at a single institution were *** neoadjuvant chemotherapy consisting of platinum,fluoropyrimidine and anthracycline was considered for operable patients(World Health Organization performance status≤2)with clinical stage T2-4 *** to neoadjuvant chemotherapy(NAC)was assessed using TRG,as described by Mandard et *** addition lymph node downstaging was also *** node downstaging was defined by cN1 at diagnosis:assessed radiologically(computed tomography,positron emission tomography,endoscopic ultrasonography),then pathologically recorded as N0 after surgery;ypN0 if NAC given prior to surgery,or pN0if surgery *** were followed up for 5 years post *** was defined radiologically,with or without pathological *** association was examined between t TRG and lymph node downstaging with disease free survival(DFS)and a comprehensive range of clinicopathological ***:Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years(median follow up:2.552,95%CI:2.022-3.081).There was a 1.8%(n=4)inpatient mortality *** hundred and thirty-six(62.4%)patients received NAC,with 74.3%(n=101)of patients demonstrating some signs of pathological tumour regression(TRG 1-4)and 5.9%(n=8)having a complete pathological *** four point one percent(n=60)had downstaging of their nodal disease(cN1 to ypN0),compared to only 15.9%(n=13)that underwent surgery alone(pre-operatively overstaged:cN1 to pN0),(P<0.0001).Response to NAC was associated with significantly increased DFS(mean DFS;TRG 1-2:5.1years,

关键词： Esophageal cancer Gastro-esophageal cancer Neoadjuvant Regression

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Surgical Management of Fracture Neck of Femur in a Medically Unfit ASA3/4 Patient Selection Using Direct Infiltration Local Anaesthesia

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Open Journal of Orthopedics 2014年第8期4卷 195-199页

作者： Tamer Kamal Sunil Garg Kareem Elsorafy Anca Duca Department of Trauma Orthopaedics Leicester Royal Infirmary Leicester UK james paget university hospital nhs foundation trust Great Yarmouth UK Robert Jones and Agnes Hunt Orthopaedic hospital Oswestry UK

Patients who suffer a Fractured Neck of Femur (NOF) have a high mortality and morbidity rate with up to 20% needing long term care post fracture and a further 30% not returning to their pre fracture functioning. Hip fracture accounts for 87% of total fragility fractures. We describe an anaesthetic technique of fixation of fracture of the femoral neck under direct infiltration local anaesthesia;that can be performed on the sick elderly patient. Twenty-eight NOF fractures were included in this series (24 DHS, 4 Hemiarthroplasty);twenty-three procedures were completed (82.14%);no patient required conversion to another form of anaesthesia either general or spinal;five patients required some degree of light sedation due to agitation (17.8%). This method presents itself as an option in managing patient with high comorbidities which can also be implemented in impoverished areas with limited access to operating surgical facilities.

关键词： Fracture Neck of Femur Local Infiltration ASA4

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Incidence of anastomotic stricture after Ivor-Lewis oesophagectomy using a circular stapling device

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World Journal of Gastrointestinal Surgery 2019年第11期11卷 407-413页

作者： Robert Tyler Amit Nair Meagan Lau james Hodson Rizwan Mahmood Jan Dmitrewski Department of Upper Gastrointestinal Surgery University Hospitals Birmingham NHS Foundation TrustBirmingham B152THUnited Kingdom Institute of Translational Medicine University Hospitals Birmingham NHS Foundation TrustBirmingham B152THUnited Kingdom Department of Gastroenterology Russells Hall HospitalDudley DY12HQUnited Kingdom

BACKGROUND Benign oesophageal strictures carry a significant level of morbidity,causing burdensome symptoms impacting on quality of ***-oesophagectomy anastomotic stricture rates as high as 41%have been reported in the *** can require endoscopic dilatation,often multiple times to relieve *** aim of the present study was to determine a single surgeons stricture rate in a series of 2-stage Ivor-Lewis procedures,and to identify any independent risk factors in their *** To determine a single surgeons stricture rate in a series of 2-stage Ivor-Lewis procedures,and to identify any independent risk factors in their *** We performed a retrospective analysis of a prospectively collected database of Ivor-Lewis oesophagectomy performed from 2004-2018 to determine the stricture *** database comprised a single-surgeon series of open,two-stage oesophagectomies with a circular stapled intra-thoracic *** location,histology,neoadjuvant chemotherapy,stapler size,T-stage and R-status were analysed to see if they could predict stricture *** was defined as dysphagia requiring endoscopic *** with anastomotic leaks were excluded on the basis they would develop an anastomotic *** One hundred and seventy patients were collected in the *** were excluded on the basis of anastomotic leak,perioperative death and early *** hundred and fifty-four patients(119 males,35 females)with a mean age of 64±10 years were eligible for analysis.A total of 15 patients developed strictures a median of 99 d(interquartile range:84-133)after surgery,giving a Kaplan-Meier estimated stricture rate of 10%at one *** of the factors considered were found to be significantly associated with *** In this study the stricture rate was 10%,with the majority occurring in the first 100 d after *** significant independent factors were found in the deve

关键词： Oesophageal cancer Anastomosis Stricture Stapled Circular

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Does Pre-Operative Tranexamic Acid Increase the Incidence of Thromboembolism in Primary Lower Limb Arthroplasty?

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Open Journal of Orthopedics 2013年第6期3卷 249-252页

作者： Veenesh Selvaratnam james R. Fountain Nigel J. Donnachie Thomas G. Thomas Fintan A. Carroll Wirral university Teaching hospital nhs foundation trust Wirral UK Wirral university Teaching hospital nhs foundation trust Wirral UK.

Introduction: Tranexamic Acid (TA) has been shown to decrease peri-operative bleeding in primary lower limb arthroplasty surgery. There are still concerns with regards to the increased risk of thromboembolic events with the use of TA. The aim of this study was to assess whether the use of pre-operative TA increased the incidence of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) in Total Hip Replacement (THR) and Total Knee Replacement (TKR). Methods: Patients who underwent primary THR or TKR between August 2007 and August 2009 were identified from the databases of three surgeons within the lower limb arthroplasty unit. A retrospective case notes analysis was performed. DVT was diagnosed on Duplex Ultrasound Scan and PE on CT Pulmonary Angiogram. A positive result was a diagnosis of DVT or PE within 3 months of surgery. Results: 701 patients underwent primary THR and TKR over the 2-year period. 320 patients (189 THR, 131 TKR) received TA pre-operatively. 381 patients (190 THR, 191 TKR) did not receive TA prior to surgery. A total of 8 (2.5%) patients who received TA were diagnosed with either a DVT (4) or PE (4) post operatively. In those patients not receiving TA, 6 had a DVT and 4 had a PE, a total of 10 (2.6%). Conclusion: Pre-operative use of Tranexamic Acid in primary THR and TKR does not increase the incidence of DVT and PE.

关键词： Tranexamic Acid DVT PE TKR THR

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Functional gastrointestinal disorders in inflammatory bowel disease: Time for a paradigm shift?

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World Journal of Gastroenterology 2020年第26期26卷 3712-3719页

作者： Dipesh H Vasant Alexander C Ford Gastroenterology Manchester University NHS Foundation TrustWythenshawe HospitalManchester M239LTUnited Kingdom Division of Diabetes Endocrinology and GastroenterologyUniversity of ManchesterManchester M239LTUnited Kingdom Leeds Institute of Medical Research at St.james’s University of LeedsLeeds LS97TFUnited Kingdom Leeds Gastroenterology Institute Leeds Teaching Hospitals NHS TrustLeeds LS97TFUnited Kingdom

Recent advances in biological therapies have revolutionalised and redefined treatment targets in inflammatory bowel disease(IBD).There is now a stronger emphasis on achieving the more stringent therapeutic goals of mucosal and histological healing,rather than clinical remission ***,the treatment of refractory“functional”gastrointestinal symptoms,often attributed as the aftermath of previous inflammation,has recently become more prominent in quiescent *** further expected advances in anti-inflammatory treatments on the horizon,the burden of such symptoms in quiescent disease,which have been relatively neglected,is set to become an even bigger *** this article,we highlight the current state of research and understanding in this field,including recent developments and clinical practice guidelines on the diagnosis and management of functional gastrointestinal symptoms,such as irritable bowel syndrome and functional anorectal and pelvic floor disorders,in patients with quiescent *** disorders are not only highly prevalent in these patients,they are often misdiagnosed,and are difficult to treat,with very few evidence-based ***,they are associated with substantial impairment in quality-of-life,considerable morbidity,and psychological *** is therefore an urgent need for a change in emphasis towards earlier recognition,positive diagnosis,and targeted treatment for patients with ongoing functional gastrointestinal symptoms in the absence of active *** article also highlights the need for further research to develop much needed evidence-based therapies.

关键词： Irritable bowel syndrome Inflammatory bowel disease Functional gastrointestinal disorders Faecal incontinence Pelvic floor dyssynergia

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An enhanced functional ability questionnaire(faVIQ) to measure the impact of rehabilitation services on the visually impaired

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International Journal of Ophthalmology(English edition) 2014年第1期7卷 77-85页

作者： james Stuart Wolffsohn Jonathan Jackson Olivia Anne Hunt Charles Cottriall Jennifer Lindsay Richard Gilmour Anne Sinclair Robert Harper Aston university Life and Health SciencesOphthalmic Research Group Australian College of Optometry Royal Victoria hospital Oxford Eye hospital Royal Victoria hospital Belfast Altnagelvin Area hospital Low Vision Clinic Fife Low Vision Centre for the Blind Manchester Royal Eye hospital and Manchester Academic and Health Science Centre Central Manchester University Hospitals NHS Foundation Trust

AIM: To develop a short,enhanced functional ability Quality of Vision(faVIQ) instrument based on previous questionnaires employing comprehensive modern statistical techniques to ensure the use of an appropriate response scale,items and scoring of the visual related difficulties experienced by patients with visual impairment. · METHODS: Items in current quality-of-life questionnaires for the visually impaired were refined by a multi-professional group and visually impaired focus groups. The resulting 76 items were completed by 293 visually impaired patients with stable vision on two occasions separated by a month. The faVIQ scores of 75 patients with no ocular pathology were compared to 75 age and gender matched patients with visual impairment. ·RESULTS: Rasch analysis reduced the faVIQ items to 27. Correlation to standard visual metrics was moderate(r =0.32-0.46) and to the NEI-VFQ was 0.48. The faVIQ was able to clearly discriminate between age and gender matched populations with no ocular pathology and visual impairment with an index of 0.983 and 95% sensitivity and 95% specificity using a cut off of 29.·CONCLUSION: The faVIQ allows sensitive assessment of quality-of-life in the visually impaired and should support studies which evaluate the effectiveness of low vision rehabilitation services.

关键词： quality of life visual impairment low vision functional ability sensitivity specificity

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Terlipressin and hepatorenal syndrome: What is important for nephrologists and hepatologists

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World Journal of Gastroenterology 2010年第41期16卷 5139-5147页

作者： Ahmed A Magan Atif A Khalil Mohamed H Ahmed Department of Surgery Cambridge Uni-versity Hospital NHS foundation Trust Hills Road Cambridge CB2 0QQ United Kingdom Department of Nephrology Royal Liverpool and Broadgreen University Hospitals Liverpool L7 8XP United Kingdom Division of Acute Medicine James Cook University Hospital Marton Road Middlesbrough TS4 3BW United Kingdom

Hepatorenal syndrome (HRS) is a reversible form of functional renal failure that occurs with advanced hepatic cirrhosis and liver failure. Despite mounting research in HRS, its etiology and medical therapy has not been resolved. HRS encompasses 2 distinct types. Type 1 is characterized by the rapid development of renal failure that occurs within 2 wk and involves a doubling of initial serum creatinine. Type 2 has a more insidious onset and is often associated with ascites. Animal studies have shown that both forms, in particular type 1 HRS, are often precipitated by bacterial infections and cir-culatory changes. The prognosis for HRS remains very poor. Type 1 and 2 both have an expected survival time of 2 wk and 6 mo, respectively. Progression of liver cir-rhosis and the resultant portal hypertension leads to the pooling of blood in the splanchnic vascular bed. The ensuing hyperdynamic circulation causes an ineffective circulatory volume which subsequently activates neuro-hormonal systems. Primarily the sympathetic nervoussystem and the renin angiotensin system are activated, which, in the early stages of HRS, maintain adequate circulation. Both advanced cirrhosis and prolonged ac-tivation of neurohormonal mechanisms result in fatal complications. Locally produced nitric oxide may have the potential to induce a deleterious vasodilatory effect on the splanchnic circulation. Currently medical therapy is aimed at reducing splanchnic vasodilation to resolve the ineffective circulation and maintain good renal per-fusion pressure. Terlipressin, a vasopressin analogue, has shown potential benefit in the treatment of HRS. It prolongs both survival time and has the ability to re-verse HRS in the majority of patients. In this review we aim to focus on the pathogenesis of HRS and its treatment with terlipressin vs other drugs.

关键词： Heptorenal syndrome Terlipressin Kidney Liver

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