24 results on '"Laing RW"'
Search Results
2. A blinded, randomised controlled trial of neo-adjuvant Celecoxib in patients with localised prostate cancer
- Author
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Sooriakumaran, P, Langley, SEM, Laing, RW, Coley, HM, Fox, SB, and Eden, C
- Published
- 2016
3. Upper gastrointestinal training in the UK and Ireland: a Roux Group Study.
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Robinson D, Zakeri R, Brown LR, Laing RW, Choh C, Askari A, Abouelazayem M, Bradley A, Currie AC, Elmasry M, Evans R, Gall T, Jerome E, Raftery NB, Samuel M, Spiers H, and Chan B
- Subjects
- Humans, United Kingdom, Ireland, Surveys and Questionnaires, Clinical Competence, Endoscopy, Gastrointestinal education, Endoscopy, Gastrointestinal statistics & numerical data, Robotic Surgical Procedures education, Robotic Surgical Procedures statistics & numerical data, Attitude of Health Personnel, Education, Medical, Graduate
- Abstract
Introduction: Surgical training programmes in the United Kingdom and Ireland (UK&I) are in a state of flux. This study aims to report the contemporary opinions of trainee and consultant surgeons on the current upper gastrointestinal (UGI) training model in the UK&I., Methods: A questionnaire was developed and distributed via national UGI societies. Questions pertained to demographics, current training evaluation, perceived requirements and availability., Results: A total of 241 responses were received with representation from all UK&I postgraduate training regions. The biggest discrepancies between rotation demand and national availability related to advanced/therapeutic endoscopy and robotic surgery, with 91.7% of respondents stating they would welcome greater geographical flexibility in training. The median suggested academic targets were 3-5 publications (trainee vs consultant <3 vs 3-5, p <0.001); <3 presentations (<3 vs 3-5, p =0.002); and 3-5 audits/quality improvement projects (<3 vs 3-5, p <0.001). Current operative requirements were considered achievable (87.6%) but inadequate for day one consultant practice (74.7%). Reassuringly, 76.3% deemed there was role for on-the-job operative training following consultant appointment. Proficiency in diagnostic endoscopy was considered a minimum requirement for Certificate of Completion of Training (CCT) yet the majority regarded therapeutic endoscopy competency as non-essential. The median numbers of index UGI operations suggested were comparable with the current curriculum requirements. Post-CCT fellowships were not considered necessary; however, the majority (73.6%) recognised their advantage., Conclusions: Current CCT requirements are largely consistent with the opinions of the UGI community. Areas for improvement include flexibility in geographical working and increasing national provisions for high-quality endoscopy training.
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- 2024
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4. Preoperative C-Reactive Protein-to-Albumin Ratio and Its Ability to Predict Outcomes of Pancreatic Cancer Resection: A Systematic Review.
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Hajibandeh S, Hajibandeh S, Romman S, Parente A, Laing RW, Satyadas T, Subar D, Aroori S, Bhatt A, Durkin D, Athwal TS, and Roberts KJ
- Abstract
Objectives: To evaluate the ability of the c-reactive protein-to-albumin ratio (CAR) in predicting outcomes in patients undergoing pancreatic cancer resection., Methods: A systematic search of electronic information sources and bibliographic reference lists was conducted. Survival outcomes and perioperative morbidity were the evaluated outcome parameters., Results: Eight studies reporting a total of 1056 patients undergoing pancreatic cancer resection were identified. The median cut-off value for CAR was 0.05 (range 0.0003-0.54). Using multivariate analysis, all studies demonstrated that a higher CAR value was an independent and significant predictor of poor overall survival in patients undergoing pancreatic cancer resection. The estimated hazard ratio (HR) ranged from 1.4 to 3.6. Although there was a positive correlation between the reported cut-off values for CAR and HRs for overall survival, it was weak and non-significant (r = 0.36, n = 6, p = 0.480). There was significant between-study heterogeneity., Conclusions: Preoperative CAR value seems to be an important prognostic score in predicting survival outcomes in patients undergoing pancreatic cancer resection. However, the current evidence does not allow the determination of an optimal cut-off value for CAR, considering the heterogeneous reporting of cut-off values by the available studies and the lack of knowledge of their sensitivity and specificity. Future research is required.
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- 2023
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5. Comment on Long-Term Normothermic Machine Preservation of Partial Livers: First Experience With 21 Human Hemi-Livers.
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Mergental H, Stephenson BT, Laing RW, Muiesan P, Perera MTP, Afford SC, and Mirza DF
- Abstract
Competing Interests: Conflict of interests disclosure DFM holds shares in the OrganOx Limited company. None of the other authors have any conflict of interest to disclose.
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- 2022
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6. Is Hepatocyte Necrosis a Good Marker of Donor Liver Viability During Machine Perfusion?
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Neil DAH, Mergental H, Hann A, Laing RW, Hartog H, Mirza DF, and Perera MTPR
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- Hepatocytes, Humans, Liver, Living Donors, Necrosis, Perfusion, Liver Transplantation
- Published
- 2022
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7. Reply to 'Hypothermic machine perfusion before viability testing of previously discarded human livers'.
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Mergental H, Laing RW, Afford SC, and Mirza DF
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- Humans, Perfusion, Liver, Liver Transplantation
- Published
- 2021
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8. The Delivery of Multipotent Adult Progenitor Cells to Extended Criteria Human Donor Livers Using Normothermic Machine Perfusion.
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Laing RW, Stubblefield S, Wallace L, Roobrouck VD, Bhogal RH, Schlegel A, Boteon YL, Reynolds GM, Ting AE, Mirza DF, Newsome PN, Mergental H, and Afford SC
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- Biomarkers, Cell- and Tissue-Based Therapy, Chemokines metabolism, Combined Modality Therapy, Cytokines metabolism, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Immunophenotyping, Immunotherapy, Organ Preservation methods, Perfusion, Proteome, Adult Stem Cells cytology, Adult Stem Cells metabolism, Liver Transplantation methods, Living Donors, Stem Cell Transplantation methods
- Abstract
Background: Pre-clinical research with multi-potent adult progenitor cells (MAPC® cells, Multistem, Athersys Inc., Cleveland, Ohio) suggests their potential as an anti-inflammatory and immunomodulatory therapy in organ transplantation. Normothermic machine perfusion of the liver (NMP-L) has been proposed as a way of introducing therapeutic agents into the donor organ. Delivery of cellular therapy to human donor livers using this technique has not yet been described in the literature. The primary objectives of this study were to develop a technique for delivering cellular therapy to human donor livers using NMP-L and demonstrate engraftment. Methods: Six discarded human livers were perfused for 6 h at 37°C using the Liver Assist (Organ Assist, Groningen). 50 × 106 CMPTX-labeled MAPC cells were infused directly into the right lobe via the hepatic artery (HA, n = 3) or portal vein (PV, n = 3) over 20 min at different time points during the perfusion. Perfusion parameters were recorded and central and peripheral biopsies were taken at multiple time-points from both lobes and subjected to standard histological stains and confocal microscopy. Perfusate was analyzed using a 35-plex multiplex assay and proteomic analysis. Results: There was no detrimental effect on perfusion flow parameters on infusion of MAPC cells by either route. Three out of six livers met established criteria for organ viability. Confocal microscopy demonstrated engraftment of MAPC cells across vascular endothelium when perfused via the artery. 35-plex multiplex analysis of perfusate yielded 13 positive targets, 9 of which appeared to be related to the infusion of MAPC cells (including Interleukin's 1b, 4, 5, 6, 8, 10, MCP-1, GM-CSF, SDF-1a). Proteomic analysis revealed 295 unique proteins in the perfusate from time-points following the infusion of cellular therapy, many of which have strong links to MAPC cells and mesenchymal stem cells in the literature. Functional enrichment analysis demonstrated their immunomodulatory potential. Conclusion: We have demonstrated that cells can be delivered directly to the target organ, prior to host immune cell population exposure and without compromising the perfusion. Transendothelial migration occurs following arterial infusion. MAPC cells appear to secrete a host of soluble factors that would have anti-inflammatory and immunomodulatory benefits in a human model of liver transplantation., (Copyright © 2020 Laing, Stubblefield, Wallace, Roobrouck, Bhogal, Schlegel, Boteon, Reynolds, Ting, Mirza, Newsome, Mergental and Afford.)
- Published
- 2020
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9. Transplantation of discarded livers following viability testing with normothermic machine perfusion.
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Mergental H, Laing RW, Kirkham AJ, Perera MTPR, Boteon YL, Attard J, Barton D, Curbishley S, Wilkhu M, Neil DAH, Hübscher SG, Muiesan P, Isaac JR, Roberts KJ, Abradelo M, Schlegel A, Ferguson J, Cilliers H, Bion J, Adams DH, Morris C, Friend PJ, Yap C, Afford SC, and Mirza DF
- Subjects
- Aged, Female, Humans, Liver metabolism, Male, Middle Aged, Non-Randomized Controlled Trials as Topic, Organ Preservation statistics & numerical data, Perfusion methods, Prospective Studies, Survival Analysis, Temperature, Time Factors, Tissue and Organ Harvesting methods, Tissue and Organ Harvesting statistics & numerical data, Graft Survival physiology, Liver physiology, Liver Function Tests methods, Liver Transplantation methods, Organ Preservation methods, Tissue Donors statistics & numerical data
- Abstract
There is a limited access to liver transplantation, however, many organs are discarded based on subjective assessment only. Here we report the VITTAL clinical trial (ClinicalTrials.gov number NCT02740608) outcomes, using normothermic machine perfusion (NMP) to objectively assess livers discarded by all UK centres meeting specific high-risk criteria. Thirty-one livers were enroled and assessed by viability criteria based on the lactate clearance to levels ≤2.5 mmol/L within 4 h. The viability was achieved by 22 (71%) organs, that were transplanted after a median preservation time of 18 h, with 100% 90-day survival. During the median follow up of 542 days, 4 (18%) patients developed biliary strictures requiring re-transplantation. This trial demonstrates that viability testing with NMP is feasible and in this study enabled successful transplantation of 71% of discarded livers, with 100% 90-day patient and graft survival; it does not seem to prevent non-anastomotic biliary strictures in livers donated after circulatory death with prolonged warm ischaemia.
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- 2020
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10. Correction: The impact on the bioenergetic status and oxidative-mediated tissue injury of a combined protocol of hypothermic and normothermic machine perfusion using an acellular haemoglobin-based oxygen carrier: The cold-to-warm machine perfusion of the liver.
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Boteon YL, Laing RW, Schlegel A, Wallace L, Smith A, Attard J, Bhogal RH, Reynolds G, Thamara Pr Perera M, Muiesan P, Mirza DF, Mergental H, and Afford SC
- Abstract
[This corrects the article DOI: 10.1371/journal.pone.0224066.].
- Published
- 2020
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11. The impact on the bioenergetic status and oxidative-mediated tissue injury of a combined protocol of hypothermic and normothermic machine perfusion using an acellular haemoglobin-based oxygen carrier: The cold-to-warm machine perfusion of the liver.
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Boteon YL, Laing RW, Schlegel A, Wallace L, Smith A, Attard J, Bhogal RH, Reynolds G, Perera MTPR, Muiesan P, Mirza DF, Mergental H, and Afford SC
- Subjects
- Adult, Aged, Blood Substitutes, Cadaver, Female, Humans, Liver blood supply, Liver Transplantation, Male, Middle Aged, Oxidative Stress, Reperfusion Injury prevention & control, Tissue Donors, Cold Ischemia, Energy Metabolism, Hemoglobins metabolism, Liver metabolism, Organ Preservation methods, Oxygen metabolism, Perfusion methods, Warm Ischemia
- Abstract
Introduction: The combination of hypothermic and normothermic machine perfusion (HMP+NMP) of the liver provides individual benefits of both techniques, improving the rescue of marginal organs. The aim of this study was to investigate the effect on the bioenergetic status and the oxidative-mediated tissue injury of an uninterrupted combined protocol of HMP+NMP using a single haemoglobin-based oxygen carrier (HBOC)-based perfusate., Methods: Ten discarded human donor livers had either 2 hours of dual hypothermic oxygenated perfusion (D-HOPE) with sequential controlled rewarming (COR) and then NMP using the HBOC-based perfusate uninterruptedly (cold-to-warm group); or 2 hours of hypothermic oxygenated perfusion (HOPE) with an oxygen carrier-free perfusate, followed by perfusate exchange and then NMP with an HBOC-based perfusate. Markers of liver function, tissue adenosine triphosphate (ATP) levels and tissue injury were systematically assessed., Results: The hypothermic phase downregulated mitochondrial respiration and increased ATP levels in both groups. The cold-to-warm group presented higher arterial vascular resistance during rewarming/NMP (p = 0.03) with a trend of lower arterial flow (p = 0.09). At the end of NMP tissue expression of markers of reactive oxygen species production, oxidative injury and inflammation were comparable between the groups., Conclusion: The uninterrupted combined protocol of HMP+NMP using an HBOC-based perfusate-cold-to-warm MP-mitigated the oxidative-mediated tissue injury and enhanced hepatic energy stores, similarly to an interrupted combined protocol; however, it simplified the logistics of this combination and may favour its clinical applicability., Competing Interests: The machine perfusion research was funded by the Queen Elizabeth Hospital Birmingham Charity’s Liver Foundation UK. YLB is funded by the NIHR Wellcome Trust. Hemopure® was provided free of charge by Hemoglobin Oxygen Therapeutics LLC. The company has not had any role in the study design, data collection, analysis, interpretation or manuscript preparation. The authors are employees of the University Hospital Birmingham or the University of Birmingham and none of them received any payment or have any conflict of interest related to this manuscript. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2019
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12. The impact of ileal pouch-anal anastomosis on graft survival following liver transplantation for primary sclerosing cholangitis.
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Trivedi PJ, Reece J, Laing RW, Slaney E, Cooney R, Gunson BK, Kamarajah SK, Pinkney T, Thompson F, Muiesan P, Schlegel A, Hirschfield GM, Iqbal T, and Ferguson J
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- Adult, Budd-Chiari Syndrome epidemiology, Budd-Chiari Syndrome etiology, Cholangitis, Sclerosing epidemiology, Cholangitis, Sclerosing rehabilitation, Colectomy adverse effects, Colectomy methods, Colectomy rehabilitation, Colectomy statistics & numerical data, Colitis, Ulcerative epidemiology, Colitis, Ulcerative surgery, Constriction, Pathologic epidemiology, Constriction, Pathologic etiology, Female, Hepatic Artery pathology, Humans, Ileostomy adverse effects, Ileostomy methods, Ileostomy rehabilitation, Ileostomy statistics & numerical data, Incidence, Male, Middle Aged, Postoperative Complications epidemiology, Postoperative Complications etiology, Reoperation statistics & numerical data, Retrospective Studies, Thrombosis epidemiology, Thrombosis etiology, Treatment Outcome, Cholangitis, Sclerosing surgery, Graft Survival, Liver Transplantation rehabilitation, Proctocolectomy, Restorative adverse effects, Proctocolectomy, Restorative rehabilitation, Proctocolectomy, Restorative statistics & numerical data
- Abstract
Background: Liver transplantation is the only life-extending intervention for primary sclerosing cholangitis (PSC). Given the co-existence with colitis, patients may also require colectomy; a factor potentially conferring improved post-transplant outcomes., Aim: To determine the impact of restorative surgery via ileal pouch-anal anastomosis (IPAA) vs retaining an end ileostomy on liver-related outcomes post-transplantation., Methods: Graft survival was evaluated across a prospectively accrued transplant database, stratified according to colectomy status and type., Results: Between 1990 and 2016, 240 individuals with PSC/colitis underwent transplantation (cumulative 1870 patient-years until first graft loss or last follow-up date), of whom 75 also required colectomy. A heightened incidence of graft loss was observed for the IPAA group vs those retaining an end ileostomy (2.8 vs 0.4 per 100 patient-years, log-rank P = 0.005), whereas rates between IPAA vs no colectomy groups were not significantly different (2.8 vs 1.7, P = 0.1). In addition, the ileostomy group experienced significantly lower graft loss rates vs. patients retaining an intact colon (P = 0.044). The risks conferred by IPAA persisted when taking into account timing of colectomy as related to liver transplantation via time-dependent Cox regression analysis. Hepatic artery thrombosis and biliary strictures were the principal aetiologies of graft loss overall. Incidence rates for both were not significantly different between IPAA and no colectomy groups (P = 0.092 and P = 0.358); however, end ileostomy appeared protective (P = 0.007 and 0.031, respectively)., Conclusion: In PSC, liver transplantation, colectomy + IPAA is associated with similar incidence rates of hepatic artery thrombosis, recurrent biliary strictures and re-transplantation compared with no colectomy. Colectomy + end ileostomy confers more favourable graft outcomes., (© 2018 John Wiley & Sons Ltd.)
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- 2018
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13. Proof of concept: liver splitting during normothermic machine perfusion.
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Stephenson BTF, Bonney GK, Laing RW, Bhogal RH, Marcon F, Neil DAH, Perera MTPR, Afford SC, Mergental H, and Mirza DF
- Abstract
Introduction: Despite utilizing extended criteria donors, there remains a shortage of livers for transplantation. No data exists on splitting donor livers with concurrent NMP-L., Methods: A liver recovered from a donor after circulatory death was subjected to NMP-L using a red cell based fluid. During NMP-L, a 'classical' left lateral + right trisegmentectomy split was performed using an integrated bipolar/ultrasonic device. After splitting, blood flow was confirmed using Doppler ultrasound in each lobe., Results: Prior to splitting, flow rates were maintained physiologically. Lactate decreased from 13.9 to 3.0 mmol/L. Lactate before and after splitting were similar in the hepatic arteries, portal veins and IVC. Doppler ultrasound demonstrated arterial and venous waveforms in both lobes after splitting., Conclusions: 'Classical' liver splitting during NMP-L is feasible, maintaining viability of both lobes. Establishing this procedure may attenuate cold ischaemic injury, allow pre-implantation monitoring of both grafts and facilitate logistics of transplanting two grafts.
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- 2018
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14. Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial.
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Laing RW, Mergental H, Yap C, Kirkham A, Whilku M, Barton D, Curbishley S, Boteon YL, Neil DA, Hübscher SG, Perera MTPR, Muiesan P, Isaac J, Roberts KJ, Cilliers H, Afford SC, and Mirza DF
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- Feasibility Studies, Humans, Non-Randomized Controlled Trials as Topic, Perfusion methods, Practice Guidelines as Topic, Prospective Studies, Time Factors, Tissue Survival, Tissue and Organ Procurement methods, Transplant Recipients, Liver metabolism, Liver Transplantation, Organ Preservation methods, Tissue and Organ Procurement standards
- Abstract
Introduction: The use of marginal or extended criteria donor livers is increasing. These organs carry a greater risk of initial dysfunction and early failure, as well as inferior long-term outcomes. As such, many are rejected due to a perceived risk of use and use varies widely between centres. Ex situ normothermic machine perfusion of the liver (NMP-L) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres., Methods and Analysis: Viability testing and transplantation of marginal livers is an open-label, non-randomised, prospective, single-arm trial designed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival. The procured rejected livers must meet predefined criteria that objectively denote their marginal condition. The liver is subjected to NMP-L following a period of static cold storage. Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters-bile production, metabolism of glucose, a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min, a pH ≥7.30 and/or maintain a homogeneous perfusion-will be considered viable and transplanted into a suitable consented recipient. The coprimary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival., Ethics and Dissemination: The protocol was approved by the National Research Ethics Service (London-Dulwich Research Ethics Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research, Innovation and Novel Technologies Advisory Group. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications., Trial Registration Number: NCT02740608; Pre-results., Competing Interests: Competing interests: RWL and YB receive salary as Wellcome Trust research fellows., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2017
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15. Transplantation of Declined Liver Allografts Following Normothermic Ex-Situ Evaluation.
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Mergental H, Perera MT, Laing RW, Muiesan P, Isaac JR, Smith A, Stephenson BT, Cilliers H, Neil DA, Hübscher SG, Afford SC, and Mirza DF
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- Adult, Aged, Allografts, Female, Follow-Up Studies, Graft Rejection prevention & control, Humans, Liver blood supply, Liver Function Tests, Male, Middle Aged, Outcome Assessment, Health Care, Pilot Projects, Primary Graft Dysfunction prevention & control, Warm Ischemia, Liver metabolism, Liver Transplantation, Organ Preservation, Perfusion methods, Tissue Donors supply & distribution, Tissue Survival, Tissue and Organ Procurement methods
- Abstract
The demand for liver transplantation (LT) exceeds supply, with rising waiting list mortality. Utilization of high-risk organs is low and a substantial number of procured livers are discarded. We report the first series of five transplants with rejected livers following viability assessment by normothermic machine perfusion of the liver (NMP-L). The evaluation protocol consisted of perfusate lactate, bile production, vascular flows, and liver appearance. All livers were exposed to a variable period of static cold storage prior to commencing NMP-L. Four organs were recovered from donors after circulatory death and rejected due to prolonged donor warm ischemic times; one liver from a brain-death donor was declined for high liver function tests (LFTs). The median (range) total graft preservation time was 798 (range 724-951) min. The transplant procedure was uneventful in every recipient, with immediate function in all grafts. The median in-hospital stay was 10 (range 6-14) days. At present, all recipients are well, with normalized LFTs at median follow-up of 7 (range 6-19) months. Viability assessment of high-risk grafts using NMP-L provides specific information on liver function and can permit their transplantation while minimizing the recipient risk of primary graft nonfunction. This novel approach may increase organ availability for LT., (© Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.)
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- 2016
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16. Liver Transplantation Using Grafts From Donors After Circulatory Death: A Propensity Score-Matched Study From a Single Center.
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Laing RW, Scalera I, Isaac J, Mergental H, Mirza DF, Hodson J, Wilkin RJ, Perera MT, and Muiesan P
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- Adult, Donor Selection, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Tissue Donors statistics & numerical data, Treatment Outcome, Brain Death, Graft Survival, Liver Diseases surgery, Liver Transplantation methods, Propensity Score, Tissue Donors supply & distribution, Tissue and Organ Procurement methods
- Abstract
The use of livers from donation after circulatory death (DCD) is increasing, but concerns exist regarding outcomes following use of grafts from "marginal" donors. To compare outcomes in transplants using DCD and donation after brain death (DBD), propensity score matching was performed for 973 patients with chronic liver disease and/or malignancy who underwent primary whole-liver transplant between 2004 and 2014 at University Hospitals Birmingham NHS Foundation Trust. Primary end points were overall graft and patient survival. Secondary end points included postoperative, biliary and vascular complications. Over 10 years, 234 transplants were carried out using DCD grafts. Of the 187 matched DCDs, 82.9% were classified as marginal per British Transplantation Society guidelines. Kaplan-Meier analysis of graft and patient survival found no significant differences for either outcome between the paired DCD and DBD patients (p = 0.162 and p = 0.519, respectively). Aspartate aminotransferase was significantly higher in DCD recipients until 48 h after transplant (p < 0.001). The incidences of acute kidney injury and ischemic cholangiopathy were greater in DCD recipients (32.6% vs. 15% [p < 0.001] and 9.1% vs. 1.1% [p < 0.001], respectively). With appropriate recipient selection, the use of DCDs, including those deemed marginal, can be safe and can produce outcomes comparable to those seen using DBD grafts in similar recipients., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2016
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17. A randomized controlled trial investigating the effects of celecoxib in patients with localized prostate cancer.
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Sooriakumaran P, Coley HM, Fox SB, Macanas-Pirard P, Lovell DP, Henderson A, Eden CG, Miller PD, Langley SE, and Laing RW
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- Celecoxib, Cyclooxygenase Inhibitors adverse effects, Humans, Immunohistochemistry, In Situ Nick-End Labeling, Male, Pyrazoles adverse effects, Single-Blind Method, Sulfonamides adverse effects, Cyclooxygenase Inhibitors therapeutic use, Prostatic Neoplasms drug therapy, Pyrazoles therapeutic use, Sulfonamides therapeutic use
- Abstract
Unlabelled: Cyclooxygenase-2 (COX-2) is associated with tumour promotion, inhibition of apoptosis, angiogenesis and metastasis. Celecoxib, a selective COX-2 inhibitor was investigated, in patients with clinically localized prostate cancer using immunohistochemistry., Patients and Methods: Patients with cT1-2 prostate cancer (n=45) were randomized to celecoxib 400mg b.d. or no treatment for four weeks prior to radical prostatectomy. Histological sections of preoperative biopsy and matched radical prostatectomy specimens were stained for markers of cell proliferation (MIB-1/Ki-67), microvessel density (CD-31 with Weidner scoring), COX-2, apoptosis (TUNEL analysis), angiogenic factors (VEGF and KDR) and HIF-1., Results: Celecoxib decreased tumour cell proliferation, microvessel density, angiogenesis and HIF-1 whilst enhancing apoptosis. These effects approached statistical significance in a multivariate model and the cell proliferation index approached statistical significance on univariate analysis., Conclusion: In this pilot study a 4 week regimen of celecoxib resulted in measurable biological effects in prostate cancer tissue. These findings warrant further investigation.
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- 2009
18. A gene expression profiling approach assessing celecoxib in a randomized controlled trial in prostate cancer.
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Sooriakumaran P, Macanas-Pirard P, Bucca G, Henderson A, Langley SE, Laing RW, Smith CP, Laing EE, and Coley HM
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- Base Sequence, Celecoxib, DNA Primers, DNA, Complementary, Humans, Male, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Prostatic Neoplasms genetics, Single-Blind Method, Cyclooxygenase Inhibitors therapeutic use, Gene Expression Profiling, Prostatic Neoplasms drug therapy, Pyrazoles therapeutic use, Sulfonamides therapeutic use
- Abstract
Background: We performed a pilot study, looking at the COX-2 inhibitor celecoxib, on newly diagnosed prostate cancer patients in the neo-adjuvant setting using DNA microarray analysis., Patients and Methods: This was a single-blinded, randomized controlled phase II presurgical (radical prostatectomy) 28-day trial of celecoxib versus no drug in patients with localized T1-2 N0 M0 prostate cancer. cDNA microarray analysis was carried out on prostate cancer biopsies taken from freshly obtained radical prostatectomy samples. Results were confirmed by qPCR analysis of a selection of genes., Results: Multiple genes were differentially expressed in response to celecoxib treatment. Statistical analysis of microarray data indicated 24 genes were up-regulated and 4 genes down-regulated as a consequence of celecoxib treatment. Gene changes e.g. survivin, SRP72kDa, were associated with promoting apoptotic cell death, enhancement of antioxidant processes and tumour suppressor function (p73 and cyclin B1 up-regulation)., Conclusion: Celecoxib at 400 mg b.i.d. for 4 weeks perioperatively gave rise to changes in gene expression in prostate cancer tissue consistent with enhancement of apoptosis and tumour suppressor function. Given the short time interval for the duration of this study, the data are encouraging and provide a good rationale for conducting further trials of celecoxib in prostate cancer.
- Published
- 2009
19. State-of-the-art: prostate LDR brachytherapy.
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Voulgaris S, Nobes JP, Laing RW, and Langley SE
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- Dose Fractionation, Radiation, Follow-Up Studies, Humans, Male, Models, Biological, Patient Selection, Prostatectomy methods, Quality of Life, Radiotherapy Dosage, Brachytherapy methods, Prostatic Neoplasms radiotherapy
- Abstract
This article on low dose rate (LDR) prostate brachytherapy reviews long-term results, patient selection and quality of life issues. Mature results from the United States and United Kingdom are reported and issues regarding definitions of biochemical failure are discussed. Latest data comparing brachytherapy with radical prostatectomy or no definitive treatment and also the risk of secondary malignancies after prostate brachytherapy are presented. Urological parameters of patient selection and quality of life issues concerning urinary, sexual and bowel function are reviewed. The position of prostate brachytherapy next to surgery as a first-line treatment modality is demonstrated.
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- 2008
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20. Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2).
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Chua S, Smith IE, A'Hern RP, Coombes GA, Hickish TF, Robinson AC, Laing RW, O'Brien ME, Ebbs SR, Hong A, Wardley A, Mughal T, Verrill M, Dubois D, and Bliss JM
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms pathology, Breast Neoplasms surgery, Chemotherapy, Adjuvant, Combined Modality Therapy, Cyclophosphamide administration & dosage, Disease-Free Survival, Doxorubicin administration & dosage, Epirubicin administration & dosage, Female, Humans, Mastectomy, Middle Aged, Remission Induction, Treatment Outcome, Vinblastine administration & dosage, Vinblastine analogs & derivatives, Vinorelbine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy
- Abstract
Background: Vinorelbine is active and well tolerated against advanced breast cancer but there are no published efficacy studies in early breast cancer. We have therefore carried out a randomised phase III neoadjuvant trial in operable breast cancer., Patients and Methods: Patients with > or =3 cm operable breast carcinoma were randomised to receive either vinorelbine 25 mg/m(2) on days 1 and 8 and epirubicin 60 mg/m(2) on day 1, 3 weekly for six cycles (VE) or doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) i.v. on day 1, 3 weekly for six cycles (AC), prior to standard local therapy, and adjuvant endocrine therapy as appropriate., Results: A total of 451 patients were randomised. Results for AC and VE, respectively, were: overall clinical response 73% and 74%, complete clinical remission 20% and 24%, pathological complete remission 12% and 12%, mastectomy rate 52% and 55%. None of these differences were significant. Dose reduction was required in 8% for AC and 20% for VE (P <0.001) (GSCF support not used). Significantly more grade 3/4 toxicity for nausea, vomiting and alopecia (despite scalp cooling) was seen for AC compared with VE but significantly less grade 3/4 thrombophlebitis and neuropathy., Conclusions: Neoadjuvant VE is as effective as AC in early breast cancer and was better tolerated except for thrombophlebitis and neuropathy.
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- 2005
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21. A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial.
- Author
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Smith IE, A'Hern RP, Coombes GA, Howell A, Ebbs SR, Hickish TF, O'Brien ME, Mansi JL, Wilson CB, Robinson AC, Murray PA, Price CG, Perren TJ, Laing RW, and Bliss JM
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms pathology, Breast Neoplasms surgery, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Humans, Infusions, Intravenous, Injections, Intravenous, Middle Aged, Neoadjuvant Therapy, Survival Analysis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy
- Abstract
Background: To compare the efficacy of continuous infusional 5-fluorouracil (5-FU)-based chemotherapy against conventional bolus chemotherapy in the preoperative treatment of patients with large operable early breast cancer., Patients and Methods: Four hundred and twenty-six women with histologically proven 3 cm invasive early breast cancer were randomised to receive pre-operative infusional 5-FU 200 mg/m(2) by daily 24 h continuous infusion via a Hickman line for 18 weeks with epirubicin 60 mg/m(2) intravenous (i.v.) bolus on day 1 and cisplatin 60 mg/m(2) i.v. bolus on day 1, both repeating 3-weekly (infusional ECisF), or conventional bolus doxorubicin 60 mg/m(2) i.v. on day 1 and cyclophosphamide 600 mg/m(2) i.v. on day 1, both repeating 3-weekly (AC), both schedules for six courses. Patients subsequently had local therapy (surgery or radiotherapy or both) and tamoxifen 20 mg orally daily as appropriate., Results: The 5 year results for AC and infusional ECisF, respectively, were as follows: overall response, 75% and 77%; complete clinical remission, 31% and 34%; pathological complete remission (pathCR), 16% for both; and pathCR with residual ductal carcinoma in situ (DCIS), 25% and 24%. Mastectomy rates were 37% and 34%, respectively. Five-year overall survival was 74% for AC and 82% for infusional ECisF (hazard ratio 0.76, 95% confidence interval 0.51-1.13; P = 0.18). Both treatments were well tolerated. Grade III/IV lethargy, vomiting, alopecia and plantar-palmar erythema were significantly greater for infusional ECisF; grade III/IV leucopenia was significantly greater for AC., Conclusions: Preoperative continuous infusional 5-FU-based chemotherapy is no more active than conventional AC for early breast cancer; with a median 5 year follow-up, the infusion-based schedule shows a non-significant trend towards improved survival.
- Published
- 2004
- Full Text
- View/download PDF
22. Iodine seed prostate brachytherapy: an alternative first-line choice for early prostate cancer.
- Author
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Langley SE and Laing RW
- Subjects
- Humans, Male, Neoadjuvant Therapy, Patient Selection, Reproducibility of Results, Brachytherapy adverse effects, Iodine Radioisotopes therapeutic use, Prostatic Neoplasms radiotherapy
- Abstract
This article on permanent iodine-125 seed prostate brachytherapy reviews the techniques, results, and patient selection issues for early prostate cancer. The long-term 10 y results of brachytherapy from Seattle, and their reproducibility in other centres both in the USA and UK are reported. The use of hormone therapy in brachytherapy and the value of combining external beam radiotherapy with a brachytherapy implant are discussed. Reviewed comparative data show the similarity of biochemical survival in patients treated with brachytherapy, radical prostatectomy, and external beam radiotherapy. The role of brachytherapy as a first-line treatment option for patients with prostate cancer is demonstrated.
- Published
- 2004
- Full Text
- View/download PDF
23. Middle cerebral artery occlusion without craniectomy in rats. Which method works best?
- Author
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Laing RJ, Jakubowski J, and Laing RW
- Subjects
- Acute Disease, Animals, Cerebrovascular Circulation, Constriction, Rats, Rats, Wistar, Brain Ischemia etiology, Cerebral Arteries surgery, Disease Models, Animal, Electrodes, Implanted, Suture Techniques
- Abstract
Background and Purpose: Our purpose was to assess the effectiveness of middle cerebral artery occlusion in producing acute focal ischemia in the rat by the use of Koizumi's and Longa's methods, in which occlusion is achieved by passing a nylon thread into the internal carotid artery., Methods: Cerebral blood flow was measured by using the hydrogen clearance method, and the brains were examined histologically to assess ischemic damage., Results: By Koizumi's method profound reduction in cerebral blood flow was achieved in 28 of 30 rats (93%). The mean cerebral blood flow in the middle cerebral artery territory was 10.7 (95% confidence interval, 9.9-11.5) ml/100 g per minute. By Longa's method reduction in cerebral blood flow was achieved in only 29 of 52 rats (56%), and in these animals mean cerebral blood flow was 33 (95% confidence interval, 28.3-33.7) ml/100 g per minute (p < 0.001 compared with Koizumi's method). Cerebral blood flow was reduced to < 16 ml/100 g per minute in only seven animals (24%)., Conclusions: By Koizumi's method the depth of ischemia is more profound, occlusion is achieved in a much higher proportion of cases, and the incidence of perforation of the intracranial internal carotid is much less frequent than by Longa's method.
- Published
- 1993
- Full Text
- View/download PDF
24. A case of breast carcinoma in association with in vitro fertilization.
- Author
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Laing RW, Glaser MG, and Barrett GS
- Subjects
- Adult, Female, Humans, Breast Neoplasms etiology, Carcinoma, Intraductal, Noninfiltrating etiology, Fertilization in Vitro
- Published
- 1989
- Full Text
- View/download PDF
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