Journal of the Nuffield Department of Surgical Sciences最新文献

{"title":"Investigating the contribution of the unfolded protein response to prostate cancer bone metastasis","authors":"Z. Kaya","doi":"10.37707/jnds.v2i4.208","DOIUrl":"https://doi.org/10.37707/jnds.v2i4.208","url":null,"abstract":"Zeynep Kaya, John C. Christianson, Ian G. Mills, Srinivasa R. Rao, Claire M. Edwards \u0000  \u0000The majority of deaths from PCa arise following metastasis, particularly to the skeleton. ER stress and the unfolded protein response (UPR) promote primary PCa, however the contribution of the UPR to PCa bone metastasis remains unknown. The aim of this work was to determine the role of the UPR in PCa bone metastasis, focusing on the osteogenic potential of PCa cells, EMT and migration, and PCa-induced bone disease. Using paired cell lines ARCaPE and ARCaPM which differ in their epithelial (E) and mesenchymal (M) characteristics, we found that components of IRE1 and ATF6 pathways are higher in ARCaPE cells than in ARCaPM and decreased upon osteogenic differentiation of ARCaPM cells. Inhibition of the IRE1 or PERK pathway increased ALP activity in ARCaPM cells. Inhibition of specific arms of the UPR produced a varied response in EMT markers with no effect on migration of ARCaPM cells. Increasing ER stress using tunicamycin significantly reduced migration of ARCaPM cells. The bone disease associated with PCa bone metastases is driven by alterations in a complex signaling network, including the RANKL/OPG pathway and Wnt signaling. ER stress, induced by tunicamycin, decreased RANKL and Dkk1 expression and increased OPG expression in ARCaPM cells. This osteolytic response to ER stress was blocked by PERK inhibition. Taken together, my research demonstrates that the UPR has multiple effects in bone metastatic PCa cells, including a reduction in migration and in osteolytic factors following UPR activation, suggesting a novel mechanism by which the UPR may modulate PCa-induced bone disease.","PeriodicalId":184356,"journal":{"name":"Journal of the Nuffield Department of Surgical Sciences","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127883820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased circulating LDL cholesterol increases myeloma tumour burden in vivo","authors":"Beatriz Gámez","doi":"10.37707/jnds.v2i4.199","DOIUrl":"https://doi.org/10.37707/jnds.v2i4.199","url":null,"abstract":"Gámez B., Morris EV., Olechnowicz S., Sowman, A., Turner, C. and Edwards CM. \u0000  \u0000Multiple myeloma (MM) is a fatal malignancy characterized by an expansion of malignant plasma cells in the bone marrow (BM) and associated with osteolytic bone disease. MM is preceded by the benign condition, monoclonal gammopathy of undetermined significance (MGUS). Understanding MGUS progression and development of MM bone disease is key for patient management. We and others have previously demonstrated that diet-induced obesity promotes myeloma progression, but the mechanisms underlying this remain unknown. The aim of the current study was to determine the effect of dietary cholesterol on MM development. A 2% cholesterol diet was used to increase circulating LDL in mice. Mice were randomly distributed to either a) cholesterol diet 4 weeks prior to 5TGM1 MM inoculation (pretreatment) or b) cholesterol diet 4 weeks prior to MM inoculation and continued for the entire experiment (continuous). Mice on the continuous cholesterol diet had increased tumour burden, associated with an increase in lipid droplet content of MM cells. No differences in tumour burden were seen in those mice where cholesterol diet was halted at time of MM inoculation. In vitro, myeloma cells cultured with delipidated FBS had a 50% reduction in viability after 72 hours. Rich cholesterol content lipoproteins (LDL) but not VLDL could restore MM cell viability, suggesting that cholesterol is responsible for this lipid-depletion effect. Taken together, our results show that high cholesterol promotes myeloma and results in a higher lipid content in myeloma cells, ultimately increasing BM tumour burden. Pretreatment with a cholesterol diet did not alter disease progression suggesting a direct pro-tumourigenic effect of cholesterol. These results demonstrate both the detrimental effect of cholesterol on myeloma progression and the potential for dietary intervention approaches.","PeriodicalId":184356,"journal":{"name":"Journal of the Nuffield Department of Surgical Sciences","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132019909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Increased Body Mass Index and Waist to Hip Ratio with Kidney Stone Disease: a prospective analysis of 493,410 UK Biobank participants","authors":"C. Lovegrove","doi":"10.37707/jnds.v2i4.200","DOIUrl":"https://doi.org/10.37707/jnds.v2i4.200","url":null,"abstract":"Catherine E Lovegrove1,2 – catherine.lovegrove@nds.ox.ac.ukThomas Littlejohns3- thomas.littlejohns@ndph.ox.ac.ukNaomi Allen3- naomi.allen@ndph.ox.ac.ukSarah A Howles1,4- sarah.bounds@doctors.org.ukBenjamin W Turney 1,2- ben.turney@nds.ox.ac.uk \u00001 Department of Urology, Oxford University Hospitals NHS Trust, Oxford, Oxfordshire, UK2 University of Oxford Nuffield Department of Surgical Sciences, Oxford, Oxfordshire, UK3 University of Oxford Nuffield Department of Public Health, Oxford, Oxfordshire, UK4 Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK \u0000  \u0000Objectives To investigate the relationship between measures of adiposity and risk of incident kidney stone disease. \u0000Patients and methods The UK Biobank is a prospective cohort study of ~500,000 participants whose height, weight, BMI, waist circumference, hip circumference, waist:hip ratio (WHR), total fat mass, fat-free mass, body-fat percentage and percentage truncal fat were measured at enrolment with linkage to medical records. ICD-10 and OPCS codes were used to identify individuals with a new diagnosis of nephrolithiasis from 2006-2010. Individuals with a history of kidney stones or incomplete data were excluded. Multivariate Cox-proportional hazard models were used to assess associations between anthropometric measures and incident kidney stones. \u0000Results From the UK Biobank, 493,410 individuals were identified for inclusion; 3,466 developed a kidney stone during the study period. Increasing weight, BMI, waist and hip circumferences, WHR, and body and truncal fat were associated with increased risk of incident kidney stone disease. However, after adjustment for BMI, only waist circumference and WHR remained significantly associated with risk of nephrolithiasis. In overweight patients, high (men 94-102cm, women 80-88cm) waist circumference or WHR (men >0.9, women >0.85) conferred >40% increased risk of stone formation. \u0000Conclusion This study indicates that android fat distribution is independently associated with increased risk of developing nephrolithiasis. Kidney stone disease is known to be associated with hypertension, cardiovascular disease, and diabetes, all of which are linked to android body shape. Our findings provide insight into anthropometric risk factors for stone disease, will facilitate identification of patients at greatest risk of stone recurrence, and will inform prevention strategies.","PeriodicalId":184356,"journal":{"name":"Journal of the Nuffield Department of Surgical Sciences","volume":"130 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125273472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence-based Medical Leadership Development: A Systematic Review","authors":"Oscar T. Lyon","doi":"10.37707/jnds.v2i4.207","DOIUrl":"https://doi.org/10.37707/jnds.v2i4.207","url":null,"abstract":"1Alexander Mafi, 2Oscar Lyons, 3Robynne George, 4Joao Galante, 5Thomas Fordwoh, 6Jan Frich,7Jaason Geerts \u00001University of Oxford, UK, 2University of Oxford, UK, 3Royal United Hospital Bath NHS Trust,4Oxford University Hospitals NHS Trust, UK, 5University of Oxford, UK, 6University of Oslo,Norway, 7Canadian College of Health Leaders, Ottawa, Canada \u0000  \u0000Health systems invest significant resources in leadership development for physicians and other health professionals. Competent leadership is considered vital for maintaining and improving quality and patient safety. We carried out this systematic review to synthesise new empirical evidence regarding medical leadership development programme factors which are associated with outcomes at the clinical and organisational levels. \u0000117 studies were included in this systematic review. 28 studies met criteria for higher reliability studies. The median critical appraisal score according to the Medical Education Research Study Quality Instrument for quantitative studies was 8.5/18 and the median critical appraisal score according to the Jonna Briggs Institute checklist for qualitative studies was 3/10. There were recurring causes of low study quality scores related to study design, data analysis and reporting. There was considerable heterogeneity in intervention design and evaluation design. Programmes with internal or mixed faculty were significantly more likely to report organisational outcomes than programmes with external faculty only (p=0.049). Project work and mentoring increased the likelihood of organisational outcomes. No leadership development content area was particularly associated with organisational outcomes. \u0000In leadership development programmes in healthcare, external faculty should be used to supplement in-house faculty and not be a replacement for in-house expertise. To facilitate organisational outcomes, interventions should include project work and mentoring. Educational methods appear to be more important for organisational outcomes than specific curriculum content. Improving evaluation design will allow educators and evaluators to more effectively understand factors which are reliably associated with organisational outcomes of leadership development.","PeriodicalId":184356,"journal":{"name":"Journal of the Nuffield Department of Surgical Sciences","volume":"37 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114001525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relative benefits of extracorporeal shockwave lithotripsy (ESWL) compared to observation in acute renal colic","authors":"C. Lovegrove","doi":"10.37707/jnds.v2i4.201","DOIUrl":"https://doi.org/10.37707/jnds.v2i4.201","url":null,"abstract":"Miss Catherine Lovegrove1,2Mandy Spencer1Prof Ben Turney1,2Ms Naomi Neal1 \u00001 Department of Urology, Oxford University Hospitals NHS Trust, Oxford, Oxfordshire, UK2 University of Oxford Nuffield Department of Surgical Sciences, Oxford, Oxfordshire, UK \u0000  \u0000Background NICE guidance recommends patients with renal colic be offered surgical treatment, including extracorporeal shockwave lithotripsy (ESWL), within 48 hours if pain is uncontrolled or stones unlikely to pass. We compared outcomes for ureteric stone passage after ESWL with those of observation to ascertain the relative benefits of ESWL. \u0000Methods We collected data on stone location, size and number of ESWL treatments required prospectively over 18 months. Stone passage was confirmed radiologically. Data were compared with MIMIC, a multi-centre collaborative study examining spontaneous stone passage after observation alone. \u0000Results 166 patients had ESWL for ureteric stones. Median size was 6.5mm (IQR 5.0-8.0mm). 57.2% (N=95) were proximal stones. Smaller stones required fewer treatments (P=0.003). Patients with a ureteric stone <5mm required median 1.0 ESWL treatments (IQR 1.0-2.0). Ureteric stones 5-7mm had median 1.0 treatments (IQR 1.0-2.0) and stones >7mm median 2.0 treatments (IQR 1.0-2.0). Compared to MIMIC, patients with ESWL for stones <5mm were 11% more likely to achieve stone clearance (100.0% vs 89.0%, P=0.001). ESWL for 5-7mm stones had 28.1% greater clearance compared to observation (77.1% vs. 49.0%, P<0.001) and ESWL for stones >7mm 21% greater likelihood of clearance (50.0% vs. 29.0%, P<0.001). Proximal ureteric stones were 16.4% more likely to pass with ESWL than observation (68.4% vs 52%, P=0.02). Distal stones showed similar passage with ESWL (77.5%) and observation (83.0%), P=0.43. \u0000Conclusions Proximal ureteric stones and those >5mm stones benefit most from ESWL. Results aid identification of patients whose stones are less likely to pass and warrant urgent review to consider ESWL.","PeriodicalId":184356,"journal":{"name":"Journal of the Nuffield Department of Surgical Sciences","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114698801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor irradiation combined with minimally invasive surgery (vascular-targeted photodynamic therapy) enhances anti-tumour effects in preclinical prostate cancer","authors":"H. Sjoberg","doi":"10.37707/jnds.v2i4.204","DOIUrl":"https://doi.org/10.37707/jnds.v2i4.204","url":null,"abstract":"Hanna T Sjoberg, Yiannis Philippou, Anette L Magnussen, Iain DC Tullis, Esther Bridges, Andrea Chatrian, Joel Loefebvre, Ka Ho Tam, Emma A Murphy, Jens Rittscher, Dina Preise, Lilach Agemy, Tamar Yechezkel, Sean C Smart, Paul Kinchesh, Stuart Gilchrist, Danny P Allen, David A Scheiblin, Stephen J Lockett, David A Wink, Alastair D Lamb, Ian G Mills, Adrian Harris, Ruth J Muschel, Boris Vojnovic, Avigdor Scherz, Freddie C Hamdy, Richard J Bryant. \u0000  \u0000Introduction There is an important clinical need to improve the treatment of high risk localised and locally advanced prostate cancer (PCa), and to reduce the side effects of these treatments. We hypothesised that multi-modality therapy combining radiotherapy and vascular-targeted photodynamic therapy (VTP) could PCa tumour control compared against monotherapy with each of these treatments alone. This could provide proof-of-concept to take to the clinic. VTP is a minimally invasive focal surgical therapy for localised PCa, which rapidly destroys targeted tumours through vascular disruption. Tumour vasculature is characterised by vessel immaturity, increased permeability, aberrant branching and inefficient flow. Fractionated radiotherapy (FRT) alters the tumour microenvironment and promotes transient vascular normalisation. \u0000Materials and Methods We investigated whether sequential delivery of FRT followed by VTP 7 days later improves PCa tumour control compared to monotherapy with FRT or VTP alone. \u0000Results FRT induced vascular normalisation changes in PCa flank tumour allografts, improving vascular function as demonstrated using dynamic contrast enhanced magnetic resonance imaging. FRT followed by VTP significantly delayed tumour growth in flank PCa allograft pre-clinical models, compared with monotherapy with FRT or VTP alone, and improved overall survival. \u0000Conclusion Taken together, these results suggest that combining FRT and VTP could become a promising multimodal clinical strategy in PCa therapy. This provides proof-of-concept for this multi-modality therapy approach to take forward to early phase clinical trials.","PeriodicalId":184356,"journal":{"name":"Journal of the Nuffield Department of Surgical Sciences","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129813944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NDS Virtual Research Away Day Programme 22nd April 2021","authors":"NDS away day organising committee","doi":"10.37707/jnds.v2i4.211","DOIUrl":"https://doi.org/10.37707/jnds.v2i4.211","url":null,"abstract":"  \u0000 ","PeriodicalId":184356,"journal":{"name":"Journal of the Nuffield Department of Surgical Sciences","volume":"113 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123684502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Foreword from the Editor-in-Chief","authors":"A. Handa","doi":"10.37707/jnds.v2i3.175","DOIUrl":"https://doi.org/10.37707/jnds.v2i3.175","url":null,"abstract":"Trinity term 2021","PeriodicalId":184356,"journal":{"name":"Journal of the Nuffield Department of Surgical Sciences","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122334392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prof Kokila Lakhoo","authors":"Solveig Hoppe","doi":"10.37707/jnds.v2i3.163","DOIUrl":"https://doi.org/10.37707/jnds.v2i3.163","url":null,"abstract":"","PeriodicalId":184356,"journal":{"name":"Journal of the Nuffield Department of Surgical Sciences","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131307526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total pancreatectomy with islet autotransplantation – a new pain management strategy in chronic pancreatitis?","authors":"Anna Chelchowska, Michael A. Silva","doi":"10.37707/jnds.v2i3.123","DOIUrl":"https://doi.org/10.37707/jnds.v2i3.123","url":null,"abstract":"I haven't attached an abstract, since the author guidelines page says: \"An abstract is not required for the surgical case study\".","PeriodicalId":184356,"journal":{"name":"Journal of the Nuffield Department of Surgical Sciences","volume":"30 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125771680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}