Zeynep Kaya, John C. Christianson, Ian G. Mills, Srinivasa R. Rao, Claire M. Edwards The 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.
Zeynep Kaya, John C. Christianson, Ian G. Mills, Srinivasa R. Rao, Claire M. Edwards，大多数前列腺癌的死亡发生在转移后，特别是转移到骨骼。内质网应激和未折叠蛋白反应(UPR)促进原发性前列腺癌，但UPR对前列腺癌骨转移的贡献尚不清楚。这项工作的目的是确定UPR在PCa骨转移中的作用，重点关注PCa细胞的成骨潜能、EMT和迁移以及PCa诱导的骨病。利用上皮细胞(E)和间充质细胞(M)特征不同的配对细胞系ARCaPE和ARCaPM，我们发现ARCaPE细胞中的IRE1和ATF6通路成分高于ARCaPM细胞，并在ARCaPM细胞成骨分化时降低。抑制IRE1或PERK通路可增加ARCaPM细胞的ALP活性。抑制UPR的特定臂在EMT标记物中产生不同的反应，但对ARCaPM细胞的迁移没有影响。tunicamycin增加内质网应激可显著降低ARCaPM细胞的迁移。与PCa骨转移相关的骨病是由一个复杂信号网络的改变驱动的，包括RANKL/OPG通路和Wnt信号。tunicamycin诱导的内质网应激降低了ARCaPM细胞中RANKL和Dkk1的表达，增加了OPG的表达。这种内质网应激的溶骨反应被PERK抑制所阻断。综上所述，我的研究表明，UPR对骨转移性PCa细胞有多种影响，包括在UPR激活后减少迁移和溶骨因子，这表明UPR可能调节PCa诱导的骨病的新机制。
{"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}
Gámez B., Morris EV., Olechnowicz S., Sowman, A., Turner, C. and Edwards CM. Multiple 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.
{"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}
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 1 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 Objectives To investigate the relationship between measures of adiposity and risk of incident kidney stone disease. Patients 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. Results 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. Conclusion 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.
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 1英国牛津郡牛津大学附属医院NHS信托泌尿科2英国牛津郡牛津大学纳菲尔德外科学系3英国牛津大学纳菲尔德公共卫生学系，牛津，牛津大学拉德克利夫医学系学术内分泌组，牛津，英国目的研究肥胖测量与肾结石发病风险之间的关系。患者和方法英国生物银行是一项前瞻性队列研究，约500,000名参与者的身高、体重、BMI、腰围、臀围、腰臀比(WHR)、总脂肪量、无脂肪量、体脂率和躯干脂肪百分比在入组时进行测量，并与医疗记录相关联。使用ICD-10和OPCS代码对2006-2010年新诊断的肾结石患者进行识别。排除有肾结石病史或资料不完整者。多变量cox -比例风险模型用于评估人体测量值与肾结石发生率之间的关系。结果来自UK Biobank, 493410人被确定纳入;在研究期间，有3466人患上了肾结石。体重、身体质量指数、腰围和臀围、腰臀比、身体和躯干脂肪的增加与发生肾结石疾病的风险增加有关。然而，在调整BMI后，只有腰围和腰宽比仍然与肾结石的风险显著相关。在超重患者中，高腰围(男性94-102cm，女性80-88cm)或腰宽比(男性>0.9，女性>0.85)使结石形成的风险增加40%以上。结论:脂肪分布与肾结石发生风险增加独立相关。众所周知，肾结石疾病与高血压、心血管疾病和糖尿病有关，所有这些疾病都与机器人体型有关。我们的研究结果为结石疾病的人体测量危险因素提供了见解，将有助于识别结石复发风险最高的患者，并为预防策略提供信息。
{"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}
1Alexander Mafi, 2Oscar Lyons, 3Robynne George, 4Joao Galante, 5Thomas Fordwoh, 6Jan Frich,7Jaason Geerts 1University 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 Health 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. 117 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. In 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.
{"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}
Miss Catherine Lovegrove1,2Mandy Spencer1Prof Ben Turney1,2Ms Naomi Neal1 1 Department of Urology, Oxford University Hospitals NHS Trust, Oxford, Oxfordshire, UK2 University of Oxford Nuffield Department of Surgical Sciences, Oxford, Oxfordshire, UK Background 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. Methods 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. Results 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. Conclusions 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.
{"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}
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. Introduction 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. Materials 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. Results 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. Conclusion 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.
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 yeechezkel, 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。改善高风险的局部和局部晚期前列腺癌(PCa)的治疗并减少这些治疗的副作用是一个重要的临床需求。我们假设多模式治疗结合放疗和血管靶向光动力治疗(VTP)比单独使用这些治疗的单一治疗更能控制PCa肿瘤。这可以为临床提供概念验证。VTP是一种用于局部PCa的微创局灶性手术治疗方法，它通过血管破坏快速破坏靶向肿瘤。肿瘤血管系统的特征是血管不成熟、通透性增加、分支异常和流动效率低下。分割放疗(FRT)改变肿瘤微环境，促进短暂的血管正常化。材料和方法我们研究了与FRT或VTP单药治疗相比，顺序给予FRT和VTP 7天后是否能改善前列腺癌的肿瘤控制。结果动态增强磁共振成像显示，FRT诱导PCa侧腹同种异体肿瘤移植物血管正常化改变，改善血管功能。与FRT或VTP单药治疗相比，FRT加VTP显著延缓了侧腹PCa异体移植临床前模型的肿瘤生长，并提高了总生存期。综上所述，这些结果表明，结合FRT和VTP可能成为PCa治疗中有希望的多模式临床策略。这为这种多模式治疗方法进入早期临床试验提供了概念证明。
{"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}
I haven't attached an abstract, since the author guidelines page says: "An abstract is not required for the surgical case study".
我没有附上摘要，因为作者指南页面上说:“外科病例研究不需要摘要”。
{"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}
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