Search results
Found 12277 matches for
The Nuffield Department of Surgical Sciences is the academic department of surgery at the University of Oxford, and hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training.
Associations of circulating retinol, vitamin E, and 1,25-dihydroxyvitamin D with prostate cancer diagnosis, stage, and grade.
PURPOSE: Some epidemiological studies suggest that vitamin A (retinol), vitamin E, and vitamin D (total 25-hydroxyvitamin D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)(2)D) are protective against prostate cancer. However, the evidence is not conclusive, with positive and null associations reported for all three vitamins. Limitations of previous studies include small sample size, lack of population controls, and reliance on self-reported dietary intake. Few studies have explored the interactions of circulating 25(OH)D with 1,25(OH)(2)D or retinol, which are biologically plausible interactions. METHODS: We investigated the associations of circulating retinol, vitamin E, and 1,25(OH)(2)D with PSA-detected prostate cancer risk, stage, and grade in a case-control study nested within the Prostate Testing for Cancer and Treatment (ProtecT) trial. We investigated the possibility of an interaction between 25(OH)D and 1,25(OH)(2)D and whether the previously observed association between 25(OH)D and prostate cancer may be modified by retinol levels. RESULTS: We included 1,433 prostate cancer cases and 1,433 healthy controls. There was no evidence of associations of circulating retinol, vitamin E, or 1,25(OH)(2)D with overall prostate cancer risk, stage (advanced vs localized), or Gleason grade (high- (≥7) vs low (<7) grade). There was no evidence of an interaction of 1,25(OH)(2)D and 25(OH)D with prostate cancer risk, stage, or grade (p interaction ≥ 0.24). The association between 25(OH)D and prostate cancer did not differ by retinol level (p interaction = 0.34). CONCLUSIONS: We found no evidence that retinol, vitamin E, or 1,25(OH)(2)D concentrations were associated with overall prostate cancer risk or more aggressive prostate cancer phenotypes. There was no evidence of an interaction between 25(OH)D and 1,25(OH)(2)D or retinol.
Neurophysiological characteristics in the periventricular/periaqueductal gray correlate with pain perception, sensation, and affect in neuropathic pain patients.
The periventricular/periaqueductal gray (PAG/PVG) is critical for pain perception and is associated with the emotional feelings caused by pain. However, the electrophysiological characteristics of the PAG/PVG have been little investigated in humans with chronic pain. The present study analyzed the oscillatory characteristics of local field potentials (LFPs) in the PAG/PVG of eighteen neuropathic pain patients. Power spectrum analysis and neural state analysis were applied to the PAG/PVG LFPs. Neural state analysis is based on a dynamic neural state identification approach and discriminates the LFPs into different neural states, including a single neural state based on one oscillation and a combinational neural state based on two paired oscillations. The durations and occurrence rates were used to quantify the dynamic features of the neural state. The results show that the combined neural state forms three local networks based on neural oscillations that are responsible for the perceptive, sensory, and affective components of pain. The first network is formed by the interaction of the delta oscillation with other oscillations and is responsible for the coding of pain perception. The second network is responsible for the coding of sensory pain information, uses high gamma as the main node, and is widely connected with other neural oscillations. The third network is responsible for the coding of affective pain information, and beta oscillations play an important role in it. This study suggested that the combination of two neural oscillations in the PAG/PVG is essential for encoding perceptive, sensory, and affective measures of pain.
The Use of Intraoperative Transit Time Flow Measurement for Coronary Artery Bypass Surgery: Systematic Review of the Evidence and Expert Opinion Statements.
Transit time flow measurement (TTFM) allows quality control in coronary artery bypass grafting but remains largely underused, probably because of limited information and the lack of standardization. We performed a systematic review of the evidence on TTFM and other methods for quality control in coronary artery bypass grafting following PRISMA standards and elaborated expert recommendations by using a structured process. A panel of 19 experts took part in the consensus process using a 3-step modified Delphi method that consisted of 2 rounds of electronic voting and a final face-to-face virtual meeting. Eighty percent agreement was required for acceptance of the statements. A 2-level scale (strong, moderate) was used to grade the statements based on the perceived likelihood of a clinical benefit. The existing evidence supports an association between TTFM readings and graft patency and postoperative clinical outcomes, although there is high methodological heterogeneity among the published series. The evidence is more robust for arterial, rather than venous, grafts and for grafts to the left anterior descending artery. Although TTFM use increases the duration and the cost of surgery, there are no data to quantify this effect. Based on the systematic review, 10 expert statements for TTFM use in clinical practice were formulated. Six were approved at the first round of voting, 3 at the second round, and 1 at the virtual meeting. In conclusion, although TTFM use may increase the costs and duration of the procedure and requires a learning curve, its cost/benefit ratio seems largely favorable, in view of the potential clinical consequences of graft dysfunction. These consensus statements will help to standardize the use of TTFM in clinical practice and provide guidance in clinical decision-making.
Optimization of SPIO Injection for Sentinel Lymph Node Dissection in a Rat Model.
The magnetic technique, consisting of a magnetic tracer and a handheld magnetometer, is a promising alternative technique for sentinel lymph node dissection (SLND) and was shown to be non-inferior to the standard technique in terms of identification rates. In this study, injection characteristics (iron dose, dilution, time course and massaging) were evaluated to optimize magnetic tracer uptake in the sentinel lymph nodes (SLN) in a rat hindleg model. 202 successful SLNDs were performed. Iron uptake in the SLN is proportional (10% utilization rate) to the injection dose between 20 and 200 μg, showing a plateau uptake of 80 μg in the SLN around 1000 μg injection. Linear regression showed that time had a higher impact than dilution, on the SLN iron uptake. Massaging showed no significant change in iron uptake. The amount of residual iron at the injection site was also proportional to the injection dose without any plateau. Time was a significant factor for wash-out of residual iron. From these results, preoperative injection may be advantageous for SLN detection as well as reduction in residual iron at the injection site by potential decrease in required injection dose.
What it takes to become an orthopaedic surgeon: A comparison of orthopaedic surgical training programmes in 10 countries focusing on structure and fellowship requirements.
BACKGROUND: The quality of surgical training has been highlighted as one of the most important patient safety issues in the future. Training surgeons and supporting them to do their best should be considered integral in providing optimum and safe care for the individual patient and the best possible return on investment in training medical professionals. In 2011, an international consensus statement defined fundamental principles for surgical training. PURPOSE: This study examines orthopaedic surgical training to explore the similarities and differences in the requirements for trainees to obtain board certification in ten countries. METHODS: Countries of the Commonwealth Health Care Comparison: Canada, the United Kingdom, the United States of America, Australia, New Zealand, Germany, France, the Netherlands, Norway and Switzerland were chosen to be compared. The relevant information was extracted from official information from authorities and administrative bodies. RESULTS: The study revealed significant differences in duration, organisation and assessment of training. So-called "competency-based" training is not featured in every country, and the manner of its implementation is variable. In particular, the numbers in surgical cases required to be accredited varies by country ranging from 1260 (UK) to 340 (Norway). CONCLUSION: Despite the recommendation in 2011 for some degree of uniformity across surgical training in industrialised countries, evidence suggests wide variation in the training programmes which is likely to be a concern in both quality of training as well as present and future patient safety.
Liquid biopsy in cholangiocarcinoma: Current status and future perspectives.
Cholangiocarcinoma (CCA) are a heterogeneous group of tumors in terms of aetiology, natural history, morphological subtypes, molecular alterations and management, but all sharing complex diagnosis, management, and poor prognosis. Several mutated genes and epigenetic changes have been detected in CCA, with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets. Accessing tumoral components and genetic material is therefore crucial for the diagnosis, management and selection of targeted therapies; but sampling tumor tissue, when possible, is often risky and difficult to be repeated at different time points. Liquid biopsy (LB) represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples. Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated, allowing a real-time monitoring of the tumor genetic profile or the response to therapy. In this review, we analysis the current evidence on the possible roles of LB (circulating DNA, circulating RNA, exosomes, cytokines) in the diagnosis and management of patients affected by CCA.
Cancer Extracellular Matrix Proteins Regulate Tumour Immunity.
The extracellular matrix (ECM) plays an increasingly recognised role in the development and progression of cancer. Whilst significant progress has been made in targeting aspects of the tumour microenvironment such as tumour immunity and angiogenesis, there are no therapies that address the cancer ECM. Importantly, immune function relies heavily on the structure, physics and composition of the ECM, indicating that cancer ECM and immunity are mechanistically inseparable. In this review we highlight mechanisms by which the ECM shapes tumour immunity, identifying potential therapeutic targets within the ECM. These data indicate that to fully realise the potential of cancer immunotherapy, the cancer ECM requires simultaneous consideration.
Proteomics analysis of the matrisome from MC38 experimental mouse liver metastases.
Dissemination of primary tumors to distant anatomical sites has a substantial negative impact on patient prognosis. The liver is a common site for metastases from colorectal cancer, and patients with hepatic metastases have generally much shorter survival, raising a need to develop and implement novel strategies for targeting metastatic disease. The extracellular matrix (ECM) is a meshwork of highly crosslinked, insoluble high-molecular-mass proteins maintaining tissue integrity and establishing cell-cell interactions. Emerging evidence identifies the importance of the ECM in cancer cell migration, invasion, intravasation, and metastasis. Here, we isolated the ECM from MC38 mouse liver metastases using our optimized method of mild detergent solubilization followed by biochemical enrichment. The matrices were subjected to label-free quantitative mass spectrometry analysis, revealing proteins highly abundant in the metastatic matrisome. The resulting list of proteins upregulated in the ECM significantly predicted survival in patients with colorectal cancer but not other cancers with strong involvement of the ECM component. One of the proteins upregulated in liver metastatic ECM, annexin A1, was not previously studied in the context of cancer-associated matrisome. Here, we show that annexin A1 was markedly upregulated in colon cancer cell lines compared with cancer cells of other origin and also over-represented in human primary colorectal lesions, as well as hepatic metastases, compared with their adjacent healthy tissue counterparts. In conclusion, our study provides a comprehensive ECM characterization of MC38 experimental liver metastases and proposes annexin A1 as a putative target for this disease.NEW & NOTEWORTHY Here, the authors provide an extensive proteomics characterization of murine colorectal cancer liver metastasis matrisome (the ensemble of all extracellular matrix molecules). The findings presented in this study may enable identification of therapeutic targets or biomarkers of hepatic metastases.
Small Bowel Tumors – Case Series Analysis: Prognostic Factors and Survivals
Small intestinal malignancy is uncommon. The clinical characteristics vary with histologic subtype, and factors predictive of outcome are not well studied. A case series analysis of clinicopathologic data from patients undergoing small intestinal malignancy resection in our institution was used over a 6-year period. Kaplan Meier survival estimates were compared using Log-rank and survival curves constructed. Multivariate analysis enabled determination of factors predictive of outcome. Eighty-seven patients were included; 24 required emergency surgery and neuroendocrine (NET) was the most common histological subtype. NETs were significantly smaller than adenocarcinomas or gastrointestinal stromal tumors (GISTs); however, a greater proportion of NETS had metastatic disease, perineural invasion and underwent R1 resection. Despite their advanced stage at presentation, NETs demonstrated favorable outcome compared with other histologic subtypes. Tumor grade, neuroendocrine histology and nodal metastasis were all independently associated with overall survival. Despite the advanced stage of NETs at presentation, these tumors demonstrated better overall survival than adenocarcinomas or GISTs. De-bulking with R1 resection is an acceptable approach for NET as compared to adenocarcinoma or GIST. Future work needs to focus on the development of targeted therapies for small intestinal adenocarcinoma to improve long-term outcome.
The Diagnostic Accuracy of Mutant KRAS Detection from Pancreatic Secretions for the Diagnosis of Pancreatic Cancer: A Meta-Analysis.
This meta-analysis aims to identify the diagnostic accuracy of mutations in the Kirsten Rat Sarcoma (KRAS) oncogene in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The survival of PDAC remains poor often due to the fact that disease is advanced at diagnosis. We analysed 22 studies, with a total of 2156 patients, to identify if the detection of KRAS mutations from pancreatic exocrine secretions yields sufficient specificity and sensitivity to detect patients with PDAC amongst healthy individuals. The majority of the studies were retrospective, samples were obtained endoscopically or surgically, and included comparator populations of patients with chronic pancreatitis and pre-malignant pancreatic lesions (PanIN) as well as healthy controls. We performed several analyses to identify the diagnostic accuracy for PDAC among these patient populations. Our results highlighted that the diagnostic accuracy of KRAS mutation for PDAC was of variable sensitivity and specificity when compared with PanINs and chronic pancreatitis, but had a higher specificity among healthy individuals. The sensitivity of this test must be improved to prevent missing early PDAC or PanINs. This could be achieved with rigorous prospective cohort studies, in which high-risk patients with normal cross-sectional imaging undergo surveillance following KRAS mutation testing.
Pentoxifylline for critical limb ischaemia
Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Protocol withdrawn due to lack of progress towards the review and topic no longer of clinical interest.
Flow Mediated Dilatation and Progression of Abdominal Aortic Aneurysms.
OBJECTIVE/BACKGROUND: Biomarker(s) for prediction of the future progression rate of abdominal aortic aneurysms (AAA) may be useful to stratify the management of individual patients. AAAs are associated with features of systemic inflammation and endothelial dysfunction. Flow mediated dilatation (FMD) of the brachial artery is a recognised non-invasive measurement for endothelial function. We hypothesised that FMD is a potential biomarker of AAA progression and reflects the temporal changes of endothelial function during AAA progression. METHODS: In a prospectively recruited cohort of patients with AAAs (Oxford Abdominal Aortic Aneurysm Study), AAA size was recorded by antero-posterior diameter (APD) (outer to outer) on ultrasound. Annual AAA progression was calculated by (ΔAPD/APD at baseline)/(number of days lapsed/365 days). FMD was assessed at the same time as AAA size measurement. Analyses of data were performed in the overall cohort, and further in subgroups of AAA by size (small: 30-39 mm; moderate: 40-55 mm; large: > 55 mm). RESULTS: FMD is inversely correlated with the diameter of AAAs in all patients (n=162, Spearman's r=-.28, p
The Experience of Patients During the Clinical Management Pathway of Abdominal Aortic Aneurysms at a NHS Trust.
Background: The epidemiology of abdominal aortic aneurysm (AAA) is changing. Outcomes for aortic surgery have improved. However, the accepted guideline for the management of AAAs has remained unchanged over the last 2 decades. We aimed to gain insight into the patients' experience while they are managed under the traditional clinical pathway. Method: With the help of a patient focus group, we designed a survey to assess the patients' perception of the disease and their experience during different stages of the AAA clinical care pathway (surveillance, perioperative care, postoperative follow-up). An invitation to participate in the survey was sent to all patients with AAA who were receiving care at the Oxford Regional Vascular Services Unit, part of the Oxford University Hospitals NHS Trust. Results: We received 194 responses from patients with AAA. One hundred seventy-seven were male, with a median age of 75 to 79 years. Just over a third had undergone surgery already, and the remaining 63% were either in surveillance or awaiting surgery. Their experience during the AAA management pathway was mostly positive. Of the issues that were most important to them in terms of their medical care, the provision of explanation and regularity of monitoring stood out as the most common considerations. Conclusion: Patients are generally satisfied with the care they received, but there is room for improvement. They have also highlighted key areas that are most important to them in terms of their medical care. These should guide the future direction for quality improvement and research.