Publications by authors named "David van Dellen"

47 Publications

Surgical management of Encapsulating Peritoneal Sclerosis (EPS) in children: international case series and literature review.

Pediatr Nephrol 2021 Aug 26. Epub 2021 Aug 26.

Department of Renal and Pancreas Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK.

Background: Encapsulating Peritoneal Sclerosis (EPS) is a rare phenomenon in paediatric patients with kidney failure treated with peritoneal dialysis (PD). This study highlights clinical challenges in the management of EPS, with particular emphasis on peri-operative considerations and surgical technique.

Methods: Retrospective analysis of all paediatric patients with EPS treated at the Manchester Centre for Transplantation.

Results: Four patients were included with a median duration of 78 months on PD. All patients had recurrent peritonitis (> 3 episodes), and all had symptoms within three months of a change of dialysis modality from PD to haemodialysis or transplant. In Manchester, care was delivered by a multi-disciplinary team, including surgeons delivering the adult EPS surgical service with a particular focus on nutritional optimisation, sepsis control, and wound management. The surgery involved laparotomy, lavage, and enterolysis of the small bowel + / - stoma formation, depending on intra-abdominal contamination. Two patients had a formal stoma, which were reversed at three and six months, respectively. Two patients underwent primary closure of the abdomen, whereas two patients had re-look procedures at 48 h with secondary closure. One patient had a post-operative wound infection, which was managed medically. One patient's stoma became detached, leading to an intra-abdominal collection requiring re-laparotomy. The median length of stay was 25 days, and patients were discharged once enteral feeding was established. All patients remained free of recurrence with normal gut function and currently two out of four have functioning transplants.

Conclusions: This series demonstrates 100% survival and parenteral feed independence following EPS surgery. Post-operative morbidity was common; however, with individualised experience-based decision-making and relevant additional interventions, patients made full recoveries. Health and development post-surgery continued, allowing the potential for transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.
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http://dx.doi.org/10.1007/s00467-021-05243-0DOI Listing
August 2021

Pre-emptive live donor kidney transplantation-moving barriers to opportunities: An ethical, legal and psychological aspects of organ transplantation view.

World J Transplant 2021 Apr;11(4):88-98

Imperial College Renal and Transplant Centre, Hammersmith Hospital, London W2 1NY, United Kingdom.

Live donor kidney transplantation (LDKT) is the optimal treatment modality for end stage renal disease (ESRD), enhancing patient and graft survival. Pre-emptive LDKT, prior to requirement for renal replacement therapy (RRT), provides further advantages, due to uraemia and dialysis avoidance. There are a number of potential barriers and opportunities to promoting pre-emptive LDKT. Significant infrastructure is needed to deliver robust programmes, which varies based on socio-economic standards. National frameworks can impact on national prioritisation of pre-emptive LDKT and supporting education programmes. Focus on other programme's components, including deceased kidney transplantation and RRT, can also hamper uptake. LDKT programmes are designed to provide maximal benefit to the recipient, which is specifically true for pre-emptive transplantation. Health care providers need to be educated to maximize early LDKT referral. Equitable access for varying population groups, without socio-economic bias, also requires prioritisation. Cultural barriers, including religious influence, also need consideration in developing successful outcomes. In addition, the benefit of pre-emptive LDKT needs to be emphasised, and opportunities provided to potential donors, to ensure timely and safe work-up processes. Recipient education and preparation for pre-emptive LDKT needs to ensure increased uptake. Awareness of the benefits of pre-emptive transplantation require prioritisation for this population group. We recommend an approach where patients approaching ESRD are referred early to pre-transplant clinics facilitating early discussion regarding pre-emptive LDKT and potential donors for LDKT are prioritized for work-up to ensure success. Education regarding pre-emptive LDKT should be the norm for patients approaching ESRD, appropriate for the patient's cultural needs and physical status. Pre-emptive transplantation maximize benefit to potential recipients, with the potential to occur within successful service delivery. To fully embrace preemptive transplantation as the norm, investment in infrastructure, increased awareness, and donor and recipient support is required.
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http://dx.doi.org/10.5500/wjt.v11.i4.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058646PMC
April 2021

Radiological initial treatment of vascular catastrophes in pancreas transplantation: Review of current literature.

Transplant Rev (Orlando) 2021 07 18;35(3):100624. Epub 2021 Apr 18.

Manchester University Hospitals NHS Foundation Trust, Department of Renal and Pancreatic Transplantation, Manchester Academic Health Science Centre, Manchester, Greater Manchester, M13 9WL, UK.

Background: Arterio-enteric fistula (AEF) is a rare but potentially devastating complication of solid organ pancreatic transplantation. Traditional management has been to remove the pancreas-duodenum allograft and control the vascular defect. Interventional radiological (IR) techniques present a new method of managing AEF related haemorrhage without re-operation and the potential to preserve graft function. This paper examines the available literature to assess efficacy and safety of this novel approach.

Methods: Aggregate results tables were constructed from 28 cases identified in the English language literature where IR was used in the management of AEF following pancreas transplantation. Outcomes recorded were death, re-bleeding, surgical intervention required and post intervention graft function. These were analysed with respect to technical factors and graft function at time of presentation.

Results: 28 cases of AEF managed by IR methods were identified. Mortality was high at 17.9%. 78.6% of all AEFs were present in failed pancreas allografts. Median time from transplant to bleeding event was 29 months. There was a trend of bleeding event occurring within 12 months of allograft failure or rejection. Of the AEFs present in functioning grafts, graft salvage rate was 33% from available data. Coil embolization or use of haemostatic compressed sponge as primary intervention was associated with a higher rate of re-bleeding and death versus arterial stenting. Arterial stenting resulted in a higher rate of distal ischaemia requiring surgical re-vascularisation. All deaths occurred in patients who did not have a transplant pancreatectomy as part of their definitive treatment.

Conclusion: IR can be an effective way to manage bleeding in the context of AEF associated with pancreas transplantation. If patient condition allows, it should be the first-choice intervention to manage AEF associated bleeding. Use of arterial stenting is more effective in controlling and preventing further bleeding. In a non-functioning graft, transplant pancreatectomy should be strongly considered, possibly in conjunction with or following arterial stenting.
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http://dx.doi.org/10.1016/j.trre.2021.100624DOI Listing
July 2021

Isiris™ for Ureteric Stent Removal in Renal Transplantation: An Initial Single-Centre Experience of 150 Cases.

Surg Innov 2021 Jun 29;28(3):366-370. Epub 2021 Mar 29.

Department of Renal & Pancreatic Transplantation, 5293Manchester University NHS Foundation Trust, Manchester, UK.

. Ureteric stent insertion is performed at the time of renal transplant to minimise the risk of post-operative urological complications, including anastomotic leak and ureteric stenosis or obstruction. Transplant ureteric stent removal (TUSR) has historically been performed via flexible cystoscopy, predominantly in a theatre setting. Isiris™ is a single-use cystoscope with integrated grasper designed for removal of ureteric stents. We report our initial experience. . A retrospective analysis of a contemporaneously maintained database was performed with review of case notes from October 2017 to September 2018. TUSR was performed by surgical middle grades with a single nurse assistant. . One hundred and fifty ureteric stents were removed in transplant recipients (mean age 50.2 years, SD ± 15.2; 61.3% male). 91.3% ( = 137) of cases were performed in the outpatient clinic. Median time to TUSR was 42 days (IQR 30-42). 147 attempts at removal were successful. One urinary tract infection (UTI) was reported following TUSR. Use of the Isiris™ for TUSR corresponds to a £63,480 saving in this cohort compared to conventional practice. This value is conservative and does not include income that has been gained from the reallocation of operating theatre capacity. . Isiris™ can safely be employed for the timely performance of non-complicated TUSR. Isiris™ releases this procedure from the confines of the operating theatre to the outpatient clinic. This reduces the resource burden for healthcare providers and may result in improved patient satisfaction. The environmental implications of disposable healthcare equipment require consideration. Evaluation of Isiris™ TUSR for encrustation is required.
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http://dx.doi.org/10.1177/15533506211007268DOI Listing
June 2021

Donor insulin therapy in intensive care predicts early outcomes after pancreas transplantation.

Diabetologia 2021 Jun 4;64(6):1375-1384. Epub 2021 Mar 4.

Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.

Aims/hypothesis: Approximately 50% of organ donors develop hyperglycaemia in intensive care, which is managed with insulin therapy. We aimed to determine the relationships between donor insulin use (DIU) and graft failure in pancreas transplantation.

Methods: UK Transplant Registry organ donor data were linked with national data from the UK solid pancreas transplant programme. All pancreas transplants performed between 2004 and 2016 with complete follow-up data were included. Logistic regression models determined associations between DIU and causes of graft failure within 3 months. Area under the receiver operating characteristic curve (aROC) and net reclassification improvement (NRI) assessed the added value of DIU as a predictor of graft failure.

Results: In 2168 pancreas transplant recipients, 1112 (51%) donors were insulin-treated. DIU was associated with a higher risk of graft loss from isolated islet failure: OR (95% CI), 1.79 (1.05, 3.07), p = 0.03, and this relationship was duration/dose dependent. DIU was also associated with a higher risk of graft loss from anastomotic leak (2.72 [1.07, 6.92], p = 0.04) and a lower risk of graft loss from thrombosis (0.62 [0.39, 0.96], p = 0.03), although duration/dose-dependent relationships were only identified in pancreas transplant alone/pancreas after kidney transplant recipients with grafts failing due to thrombosis (0.86 [0.74, 0.99], p = 0.03). The relationships between donor insulin characteristics and isolated islet failure remained significant after adjusting for potential confounders: DIU 1.75 (1.02, 2.99), p = 0.04; duration 1.08 (1.01, 1.16), p = 0.03. In multivariable analyses, donor insulin characteristics remained significant predictors of lower risk of graft thrombosis in pancreas transplant alone/pancreas after kidney transplant recipients: DIU, 0.34 (0.13, 0.90), p = 0.03; insulin duration/dose, 0.02 (0.001, 0.85), p = 0.04. When data on insulin were added to models predicting isolated islet failure, a significant improvement in discrimination and risk reclassification was observed in all models: no DIU aROC 0.56; DIU aROC 0.57, p = 0.86; NRI 0.28, p < 0.00001; insulin duration aROC 0.60, p = 0.47; NRI 0.35, p < 0.00001.

Conclusions/interpretation: DIU predicts graft survival in pancreas transplant recipients. This assessment could help improve donor selection and thereby improve patient and graft outcomes.
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http://dx.doi.org/10.1007/s00125-021-05411-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099796PMC
June 2021

A Successful Treatment of Encapsulating Peritoneal Sclerosis in an Adolescent Boy on Long-term Peritoneal Dialysis: A Case Report.

Prague Med Rep 2020 ;121(4):254-261

Department of Transplant and Endocrine Surgery, Manchester Royal Infirmary, Manchester University Foundation Trust; An United Kingdom National Specialized Centre for Surgery for Encapsulating Peritoneal Sclerosis, Manchester, United Kingdom.

Encapsulating peritoneal sclerosis (EPS) is a rare life-threatening complication associated with peritoneal dialysis (PD). EPS is characterized by progressive fibrosis and sclerosis of the peritoneum, with the formation of a membrane and tethering of loops of the small intestine resulting in intestinal obstruction. It is very rare in children. We present a case of a 16-year-old adolescent boy who developed EPS seven years after being placed on continuous ambulatory peritoneal dialysis (CAPD) complicated by several episodes of bacterial peritonitis. The diagnosis was based on clinical, radiological, intraoperative and histopathological findings. The patient was successfully treated with surgical enterolysis. During a 7-year follow-up, there have been no further episodes of small bowel obstruction documented. He still continues to be on regular hemodialysis and is awaiting a deceased donor kidney transplant. EPS is a long-term complication of peritoneal dialysis and is typically seen in adults. Rare cases may be seen in the pediatric population and require an appropriate surgical approach that is effective and lifesaving for these patients.
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http://dx.doi.org/10.14712/23362936.2020.22DOI Listing
January 2021

Kidney Transplantation From a 5-Day-Old Donor With a Single Functioning Kidney.

Exp Clin Transplant 2020 11;18(6):732-736

From the Department of Renal and Pancreas Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Unitek Kingdom.

Kidney transplant restores renal function in eligible patients with end-stage renal failure who require renal replacement therapy. There remains a significant disparity between the demand and supply of suitable kidneys for transplant. In recent years, pediatric donors have formed an important area for expansion of the donor pool. However, neonatal donation (< 28 days) remains an underutilized resource. We describe a case of en bloc kidney transplant from a 5-day-old donor after circulatory death into an adult recipient. One kidney thrombosed almost immediately, leaving a single 4.5-cm, poorly functioning kidney. Eighteen months after transplant, the recipient has shown good function with the estimated glomerular filtration rate continuing to improve. This case demonstrates that a single neonatal kidney can grow and adapt to provide adequate renal function in an adult. This experience suggests that a single kidney from a neonate can sustain renal function in adults, and every effort should be made to maximize their use in transplant.
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http://dx.doi.org/10.6002/ect.2020.0254DOI Listing
November 2020

Effect of rectus sheath block vs. spinal anaesthesia on time-to-readiness for hospital discharge after trans-peritoneal hand-assisted laparoscopic live donor nephrectomy: A randomised trial.

Eur J Anaesthesiol 2021 04;38(4):374-382

From the Department of Anaesthesia, Manchester Royal Infirmary (KB, RW, WM, CJ), Department of Anaesthesia and Intensive Care, Wythenshawe Hospital (MC) and Department of Transplant Surgery, Manchester Royal Infirmary, Manchester University Hospital NHS Foundation Trust, Manchester, UK (TC, DVD).

Background: The role of spinal anaesthesia in patients having a transperitoneal hand-assisted laparoscopic donor nephrectomy in an enhanced recovery setting has never been investigated.

Objective: We explored whether substituting a rectus sheath block (RSB) with spinal anaesthesia, as an adjunct to a general anaesthetic technique, influenced time-to-readiness for discharge in patients undergoing hand-assisted laparoscopic donor nephrectomy.

Design: Prospective randomised open blinded end-point (PROBE) study with two parallel groups.

Setting: Tertiary University Hospital.

Patients: Ninety-seven patients undergoing a trans-peritoneal hand-assisted laparoscopic donor nephrectomy.

Intervention: Patients (n=52) were randomly assigned to receive a general anaesthetic and a surgical RSB with 2 mg kg-1 of levobupivacaine at the time of surgical closure or a spinal anaesthetic with hyperbaric bupivacaine 12.5 mg and diamorphine 0.5 mg (n=45) before general anaesthesia.

Primary Outcome: The primary outcome was the time-to-readiness for discharge following surgery.

Results: Median [IQR] times-to-readiness for discharge were 75 [56 to 83] and 79 [67 to 101] h for RSB and spinal anaesthesia and there was no significant difference in times-to-readiness for discharge (median difference 4 (95% CI, 0 to 20h; P  = 0.07)). There were no significant differences in pain scores at rest (P  = 0.91) or on movement (P = 0.66). Median 24-h oxycodone consumptions were similar (P  = 0.80). Nausea and vomiting scores were similar (P = 0.57) and urinary retention occurred in one vs. four patients with RSB and spinal anaesthesia, respectively (P  = 0.077).

Conclusion: Substitution of RSB with spinal anaesthesia using 12.5 mg hyperbaric bupivacaine and 0.5 mg diamorphine, together with a general anaesthetic failed to confer any benefit on time-to-discharge readiness following transperitoneal hand-assisted laparoscopic donor nephrectomy. RSB provided similar analgesia in the immediate postoperative period with a low frequency of side-effects in this cohort.

Trial Registration: ClinicalTrial.gov identifier: NCT02700217.
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http://dx.doi.org/10.1097/EJA.0000000000001337DOI Listing
April 2021

Peri-transplant glycaemic control as a predictor of pancreas transplant survival.

Diabetes Obes Metab 2021 01 5;23(1):49-57. Epub 2020 Oct 5.

Department of Renal and Pancreas Transplantation, Manchester University NHSFT, Manchester, UK.

Aims: The relationship between peri-transplant glycaemic control and outcomes following pancreas transplantation is unknown. We aimed to relate peri-transplant glycaemic control to pancreas graft survival and to develop a framework for defining early graft dysfunction.

Methods: Peri-transplant glycaemic control profiles over the first 5 days postoperatively were determined by an area under the curve [AUC; average daily glucose level (mmol/L) × time (days)] and the coefficient of variation of mean daily glucose levels. Peri-transplant hyperglycaemia was defined as an AUC ≥35 mmol/day/L (daily mean blood glucose ≥7 mmol/L). Risks of graft failure associated with glycaemic control and variability and peri-transplant hyperglycaemia were determined using covariate-adjusted Cox regression.

Results: We collected 7606 glucose readings over 5 days postoperatively from 123 pancreas transplant recipients. Glucose AUC was a significant predictor of graft failure during 3.6 years of follow-up (unadjusted HR [95% confidence interval] 1.17 [1.06-1.30], P = .002). Death censored non-technical graft failure occurred in eight (10%) recipients with peri-transplant normoglycaemia, and eight (25%) recipients with peri-transplant hyperglycaemia such that hyperglycaemia predicted a 3-fold higher risk of graft failure [HR (95% confidence interval): 3.0 (1.1-8.0); P = .028].

Conclusion: Peri-transplant hyperglycaemia is strongly associated with graft loss and could be a valuable tool guiding individualized graft monitoring and treatment. The 5-day peri-transplant glucose AUC provides a robust and responsive framework for comparing graft function.
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http://dx.doi.org/10.1111/dom.14181DOI Listing
January 2021

A role for human leucocyte antigens in the susceptibility to SARS-Cov-2 infection observed in transplant patients.

Int J Immunogenet 2020 Aug 5;47(4):324-328. Epub 2020 Jul 5.

Transplant Immunology, St James's University Hospital, Leeds, UK.

We analysed data from 80 patients who tested positive for SARS-CoV-2 RNA who had previously been HLA typed to support transplantation. Data were combined from two adjacent centres in Manchester and Leeds to achieve a sufficient number for early analysis. HLA frequencies observed were compared against two control populations: first, against published frequencies in a UK deceased donor population (n = 10,000) representing the target population of the virus, and second, using a cohort of individuals from the combined transplant waiting lists of both centres (n = 308), representing a comparator group of unaffected individuals of the same demographic. We report a significant HLA association with HLA- DQB1*06 (53% vs. 36%; p < .012; OR 1.96; 95% CI 1.94-3.22) and infection. A bias towards an increased representation of HLA-A*26, HLA-DRB1*15, HLA-DRB1*10 and DRB1*11 was also noted but these were either only significant using the UK donor controls, or did not remain significant after correction for multiple tests. Likewise, HLA-A*02, HLA-B*44 and HLA-C*05 may exert a protective effect, but these associations did not remain significant after correction for multiple tests. This is relevant information for the clinical management of patients in the setting of the current SARS-CoV-2 pandemic and potentially in risk-assessing staff interactions with infected patients.
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http://dx.doi.org/10.1111/iji.12505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361549PMC
August 2020

The impact of the COVID-19 pandemic on renal transplantation in the UK.

Clin Med (Lond) 2020 07 25;20(4):e82-e86. Epub 2020 May 25.

Manchester University Hospitals NHS Foundation Trust, Manchester, UK and University of Manchester, Manchester, UK.

COVID-19 is impacting provision of renal transplantation in the UK with a reduction in clinical activity. Publicly available Renal Registry and NHS Blood and Transplant reports were analysed to model the number of missed transplant opportunities, waiting list size and change in dialysis population over a six-month period starting 5 March 2020. An estimated 1,670 kidney transplant opportunities may be lost, which will lead to 6,317 active patients on the kidney-alone waiting list, compared to 4,649 based on usual activity estimates. This will result in 1,324 additional patients on dialysis who would otherwise have been transplanted. COVID-19 will lead to a marked loss of transplant opportunities and a significantly larger national waiting list. The existing strain on dialysis capacity will be exacerbated as patients remain on dialysis as the only available form of renal replacement therapy. These findings will help inform policy and service specific strategies.
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http://dx.doi.org/10.7861/clinmed.2020-0183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385760PMC
July 2020

Donor insulin use predicts beta-cell function after islet transplantation.

Diabetes Obes Metab 2020 10 14;22(10):1874-1879. Epub 2020 Jun 14.

Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.

Insulin is routinely used to manage hyperglycaemia in organ donors and during the peri-transplant period in islet transplant recipients. However, it is unknown whether donor insulin use (DIU) predicts beta-cell dysfunction after islet transplantation. We reviewed data from the UK Transplant Registry and the UK Islet Transplant Consortium; all first-time transplants during 2008-2016 were included. Linear regression models determined associations between DIU, median and coefficient of variation (CV) peri-transplant glucose levels and 3-month islet graft function. In 91 islet cell transplant recipients, DIU was associated with lower islet function assessed by BETA-2 scores (β [SE] -3.5 [1.5], P = .02), higher 3-month post-transplant HbA1c levels (5.4 [2.6] mmol/mol, P = .04) and lower fasting C-peptide levels (-107.9 [46.1] pmol/l, P = .02). Glucose at 10 512 time points was recorded during the first 5 days peri-transplant: the median (IQR) daily glucose level was 7.9 (7.0-8.9) mmol/L and glucose CV was 28% (21%-35%). Neither median glucose levels nor glucose CV predicted outcomes post-transplantation. Data on DIU predicts beta-cell dysfunction 3 months after islet transplantation and could help improve donor selection and transplant outcomes.
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http://dx.doi.org/10.1111/dom.14088DOI Listing
October 2020

Living donor kidney transplantation: Let's talk about it.

Clin Med (Lond) 2020 05;20(3):346-348

Manchester University Hospitals NHS Foundation Trust, Manchester, UK and University of Manchester, Manchester, UK.

Transplantation is the preferred treatment option for end-stage renal disease as it offers superior results and patient reported outcomes in comparison to dialysis. Patients treated with a transplant live longer, healthier and more independent lives. Transplantation is also more cost-effective, reducing the overall burden of renal disease. Despite the rising incidence of renal failure, the uptake of living donor kidney transplantation has been static across the UK for several years. Among transplantation, living donation offers a number of advantages compared with deceased donor transplantation. The procedure is more likely to be performed pre-dialysis and the elective nature allows for better perioperative planning. Awareness for living donation processes among healthcare professionals, patients and the public appears to be poor. Sharing information regarding the process will help educate colleagues, dispel myths and, crucially, allow patients the opportunity to talk about this treatment option with their hospital doctor.
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http://dx.doi.org/10.7861/clinmed.2020-0047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354017PMC
May 2020

Raising awareness of unspecified living kidney donation: an ELPAT view.

Clin Kidney J 2020 Apr 15;13(2):159-165. Epub 2019 Jun 15.

Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College, London, UK.

Background: Living donor kidney transplantation (LDKT) is the preferred treatment for patients with end-stage renal disease and unspecified living kidney donation is morally justified. Despite the excellent outcomes of LDKT, unspecified kidney donation (UKD) is limited to a minority of European countries due to legal constraints and moral objections. Consequently, there are significant variations in practice and approach between countries and the contribution of UKD is undervalued. Where UKD is accepted as routine, an increasing number of patients in the kidney exchange programme are successfully transplanted when a 'chain' of transplants is triggered by a single unspecified donor. By expanding the shared living donor pool, the benefit of LDKT is extended to patients who do not have their own living donor because a recipient on the national transplant list always completes the chain. Is there a moral imperative to increase the scope of UKD and how could this be achieved?

Methods: An examination of the literature and individual country practices was performed to identify the limitations on UKD in Europe and recommend strategies to increase transplant opportunities.

Results: Primary limitations to UKD, key players and their roles and responsibilities were identified.

Conclusions: Raising awareness to encourage the public to volunteer to donate is appropriate and desirable to increase UKD. Recommendations are made to provide a framework for increasing awareness and engagement in UKD. The public, healthcare professionals, policy makers and society and religious leaders have a role to play in creating an environment for change.
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http://dx.doi.org/10.1093/ckj/sfz067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147300PMC
April 2020

Prophylaxis of Wound Infections-antibiotics in Renal Donation (POWAR): A UK Multicentre Double Blind Placebo Controlled Randomised Trial.

Ann Surg 2020 07;272(1):65-71

Department of Transplantation, Guy's & St Thomas' NHS Foundation Trust, King's College, London, UK.

Background: Postoperative infection after hand-assisted laparoscopic donor nephrectomy (HALDN) confers significant morbidity to a healthy patient group. Current UK guidelines cite a lack of evidence for routine antibiotic prophylaxis. This trial assessed if a single preoperative antibiotic dose could reduce post HALDN infections.

Methods: Eligible donors were randomly and blindly allocated to preoperative single-dose intravenous co-amoxiclav or saline. The primary composite endpoint was clinical evidence of any postoperative infection at 30 days, including surgical site infection (SSI), urinary tract infection (UTI), and lower respiratory tract infection (LRTI).

Findings: In all, 293 participants underwent HALDN (148 antibiotic arm and 145 placebo arm). Among them, 99% (291/293) completed follow-up. The total infection rate was 40.7% (59/145) in the placebo group and 23% (34 of 148) in the antibiotic group (P = 0.001). Superficial SSIs were 20.7% (30/145 patients) in the placebo group versus 10.1% (15/148 patients) in the antibiotic group (P = 0.012). LRTIs were 9% (13/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.046). UTIs were 4.1% (6/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.72).Antibiotic prophylaxis conferred a 17.7% (95% confidence interval 7.2%-28.1%), absolute risk reduction in developing postoperative infection, with 6 donors requiring treatment to prevent 1 infection.

Interpretation: Single-dose preoperative antibiotic prophylaxis dramatically reduces post-HALDN infection rates, mainly impacting SSIs and LRTIs.
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http://dx.doi.org/10.1097/SLA.0000000000003666DOI Listing
July 2020

Monthly variance in UK renal transplantation activity: a national retrospective cohort study.

BMJ Open 2019 09 17;9(9):e028786. Epub 2019 Sep 17.

Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

Objective: To identify whether renal transplant activity varies in a reproducible manner across the year.

Design: Retrospective cohort study using NHS Blood and Transplant data.

Setting: All renal transplant centres in the UK.

Participants: A total of 24 270 patients who underwent renal transplantation between 2005 and 2014.

Primary Outcome: Monthly transplant activity was analysed to see if transplant activity showed variation during the year.

Secondary Outcome: The number of organs rejected due to healthcare capacity was analysed to see if this affected transplantation rates.

Results: Analysis of national transplant data revealed a reproducible yearly variance in transplant activity. This activity increased in late autumn and early winter (p=0.05) and could be attributed to increased rates of living (October and November) and deceased organ donation (November and December). An increase in deceased donation was attributed to a rise in donors following cerebrovascular accidents and hypoxic brain injury. Other causes of death (infections and road traffic accidents) were more seasonal in nature peaking in the winter or summer, respectively. Only 1.4% of transplants to intended recipients were redirected due to a lack of healthcare capacity, suggesting that capacity pressures in the National Health Service did not significantly affect transplant activity.

Conclusion: UK renal transplant activity peaks in late autumn/winter in contrast to other countries. Currently, healthcare capacity, though under strain, does not affect transplant activity; however, this may change if transplantation activity increases in line with national strategies as the spike in transplant activity coincides with peak activity in the national healthcare system.
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http://dx.doi.org/10.1136/bmjopen-2018-028786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756352PMC
September 2019

Living donor kidney transplantation: often a missed opportunity.

Br J Gen Pract 2019 Sep 29;69(686):428-429. Epub 2019 Aug 29.

Central Manchester University Hospitals NHS Foundation Trust, Department of Renal and Pancreatic Transplantation, Manchester, UK.

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http://dx.doi.org/10.3399/bjgp19X705173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715493PMC
September 2019

Letter to Editor: Small and Laterally Placed Incisional Hernias Can Be Safely Managed with an Onlay Repair.

World J Surg 2019 11;43(11):2945-2946

Department of Renal and Pancreas Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, UK.

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http://dx.doi.org/10.1007/s00268-019-05088-7DOI Listing
November 2019

Insulin therapy in organ donation and transplantation.

Diabetes Obes Metab 2019 07 14;21(7):1521-1528. Epub 2019 Apr 14.

Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Medicine, Biology and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

Hyperglycaemia is common in hospitalized individuals, and is often caused by physiological stress associated with critical illness or major surgery. Insulin therapy is an established treatment for hyperglycaemia and acute hyperkalaemia, and has also been used for myocardial dysfunction resistant to inotropic support. Insulin is commonly used in both organ donors and transplant recipients for hyperglycaemia, but the underlying knowledge base supporting its use remains limited. Insulin therapy plays an important yet poorly understood role in both organ donation and transplantation. Tight glycaemic control has been extensively studied in critical care over the past 15 years; however, this has not yet translated into the field of transplantation, where patients are more unwell and where improved outcomes remain an ongoing challenge. Insulin therapy and optimization of glycaemic control represent important areas for future hypothesis-driven research into organ donation and transplantation, such as amelioration of ischaemia-reperfusion injury, rejection and infection.
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http://dx.doi.org/10.1111/dom.13728DOI Listing
July 2019

Major Adverse Cardiovascular Events Following Simultaneous Pancreas and Kidney Transplantation in the United Kingdom.

Diabetes Care 2019 04 14;42(4):665-673. Epub 2019 Feb 14.

Department of Renal and Pancreatic Transplantation, Manchester University NHS Foundation Trust, Manchester, U.K.

Objective: People with type 1 diabetes and kidney failure have an increased risk for major adverse cardiovascular events (MACE). Simultaneous pancreas and kidney transplantation (SPKT) improves survival, but the long-term risk for MACE is uncertain.

Research Design And Methods: We assessed the frequency and risk factors for MACE (defined as fatal cardiovascular disease and nonfatal myocardial infarction or stroke) and related nonfatal MACE to allograft failure in SPKT recipients with type 1 diabetes who underwent transplantation between 2001 and 2015 in the U.K. In a subgroup, we related a pretransplant cardiovascular risk score to MACE.

Results: During 5 years of follow-up, 133 of 1,699 SPKT recipients (7.8%) experienced a MACE. In covariate-adjusted models, age (hazard ratio 1.04 per year [95% CI 1.01-1.07]), prior myocardial infarction (2.6 [1.3-5.0]), stroke (2.3 [1.2-4.7]), amputation (2.0 [1.02-3.7]), donor history of hypertension (1.8 [1.05-3.2]), and waiting time (1.02 per month [1.0-1.04]) were significant predictors. Nonfatal MACE predicted subsequent allograft failure (renal 1.6 [1.06-2.6]; pancreas 1.7 [1.09-2.6]). In the subgroup, the pretransplant cardiovascular risk score predicted MACE (1.04 per 1% increment [1.02-1.06]).

Conclusions: We report a high rate of MACE in SPKT recipients. There are a number of variables that predict MACE, while nonfatal MACE increase the risk of subsequent allograft failure. It may be beneficial that organs from hypertensive donors are matched to recipients with lower cardiovascular risk. Pretransplant cardiovascular risk scoring may help to identify patients who would benefit from risk factor optimization or alternative transplant therapies and warrants validation nationally.
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http://dx.doi.org/10.2337/dc18-2111DOI Listing
April 2019

Laparoscopic hand-assisted adrenalectomy for tumours larger than 5 cm.

Clin Endocrinol (Oxf) 2019 01 15;90(1):74-78. Epub 2018 Nov 15.

Departments of Transplant and Endocrine Surgery, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Objective: Adrenal surgery remains a distinct surgical challenge. Technical challenges associated with laparoscopic adrenalectomy are tumour size, haemorrhage control and oncological compromise. Hand-assisted laparoscopic (HAL) adrenalectomy, utilizing a hand-port device, offers minimally invasive surgery with the advantages and safety of tactile feedback. We aimed to assess the efficacy of HAL for patients requiring adrenalectomy for tumours over 5 cm in size.

Context: Hand-assisted laparoscopic surgery is used in several surgical specialities over totally laparoscopic surgery to manage sizeable pathology, reduce operating time and conversion rates. HAL adrenalectomy is demonstrated in this series as a safe alternative to laparoscopic adrenalectomy for large adrenal tumours.

Design: A retrospective analysis of all HAL adrenalectomies performed over 8 years (October 2006-May 2015) by a single surgeon was performed. This case series is the largest study of this technique.

Patients: All patients who were fit for surgery with adrenal tumours (over 5 cm) were included.

Analysis: Primary endpoints were overall mortality, operating time, hospital stay, complications and conversion to open surgery.

Results: A total of 56 patients underwent the procedure. A total of 43 had unilateral and 13 bilateral lesions. Most lesions (45) were histologically benign. These included functioning and non-functioning tumours. Median tumour size was 8 cm (range 5-19 cm). There was one (1.8%) intra-operative conversion and no peri-operative mortality. Postoperative complications occurred in 8 (14%) patients, all self-limiting. The median length of stay was 6 days (range 2-21). There was one recurrence of pathology with repeat surgery.

Conclusion: Hand-assisted laparoscopic surgery offers a safe reproducible approach to adrenal surgery combining minimally invasive surgery with tactile integration. Although previously described in small numbers, this represents the largest case series to date. HAL is a safe minimally invasive surgical option for larger tumours, including malignancies. The HAL technique may additionally offer a shorter learning curve for trainee adrenal surgeons.
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http://dx.doi.org/10.1111/cen.13883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379292PMC
January 2019

Should End-of-Life Preferences Be Discussed Routinely before High-Risk Surgery?

J Palliat Med 2018 12 4;21(12):1818-1821. Epub 2018 Oct 4.

Department of Renal and Pancreas Transplantation, NHS England Funded UK referral center for Encapsulating Peritoneal Sclerosis Surgery, Manchester Royal Infirmary, Manchester, United Kingdom.

Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis. It is characterized by peritoneal neovascularization, fibrosis, and calcification ultimately leading to intestinal obstruction and eventual failure. Surgery for EPS has a mortality approaching 50% and most patients require some form of postoperative life-sustaining therapy (LST) during their admission. A 43-year-old gentleman with progressive EPS and significant comorbidities was assessed for enterolysis after a failed first attempt at another center. Because of his comorbidities, postoperative mortality was quoted above 50%. The patient favored surgery to improve his survival and quality of life, but was reluctant to receive prolonged LST in the event of failure of surgical therapy. The surgical team, in conjunction with a palliative care physician, therefore held extensive discussions with the patient and his partner regarding LST and its limitations. Clinical parameters to trigger a transition to palliative care were identified and agreed. Limitations on LST that are directly expressed by patients can represent a contraindication to surgery for many surgeons. is a concept described as a perceived contract, or covenant, between the patient and clinician regarding implied consent for postoperative LST. Currently, preoperative discussions regarding limitations of LST are infrequent, and there can be reticence among patients and surgeons to have these conversations, leading to dissatisfaction on behalf of the patient and their family. After the Montgomery legal ruling, the provision and perception of informed consent are particularly pertinent. The palliative care physician is uniquely placed to contribute to such discussions as part of the surgical multidisciplinary team.
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http://dx.doi.org/10.1089/jpm.2018.0048DOI Listing
December 2018

Encapsulating peritoneal sclerosis following hyperthermic intraperitoneal chemotherapy.

ANZ J Surg 2019 10 2;89(10):E468-E469. Epub 2018 Sep 2.

Division of Transplant and Endocrine Surgery, Manchester Royal Infirmary, Manchester University Foundation Trust, Manchester, UK.

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http://dx.doi.org/10.1111/ans.14770DOI Listing
October 2019

Simultaneous en-bloc pancreas and kidney transplantation from a small pediatric donor after circulatory death.

Am J Transplant 2019 03 27;19(3):929-932. Epub 2018 Aug 27.

Department of Renal and Pancreatic Transplantation, Manchester University NHS Foundation Trust, Manchester, UK.

Simultaneous pancreas and kidney transplantation (SPKT) is an effective treatment option for patients with type 1 diabetes and end stage renal disease. Increasing demands for organs for transplantation coupled with a rise in age and size of adult donors has led to greater utilization of pediatric donors, and with good outcomes. Nonetheless, there remains reticence among transplant surgeons to transplant pancreases from small pediatric donors despite the optimal characteristics and macroscopic features of the younger pancreas. We report a successful case of SPKT from a small pediatric donor and explore the aspects of potential concern that might have led some clinicians to decline these organs. We also discuss the measures taken to overcome potential obstacles to successful transplantation from this donor source, and the rationale behind them.
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http://dx.doi.org/10.1111/ajt.15044DOI Listing
March 2019

Office-based ureteric stent removal is achievable, improves clinical flexibility and quality of care, whilst also keeping surgeons close to their patients.

Cent European J Urol 2018 28;71(2):196-201. Epub 2018 Mar 28.

Central Manchester Teaching Hospital, Foundation Trust, Department of Urology, Manchester, United Kingdom.

Introduction: Diagnostic pressure on endoscopy suites can result in stent removal not receiving the required priority and unnecessary morbidity for patients. As well as using stents with extraction strings, the introduction of a portable single-use flexible cystoscope for ureteric stent removal (Isiris™), offered an opportunity to negotiate these issues by relocating stent removal to the office/clinic. This study aimed to determine whether such flexibility reduced stent dwell time with the assumption this would improve patient experience and decrease associated complications.

Materials And Methods: A retrospective review of ureteric stents placed during stone procedures was undertaken. Data collection included; patient demographics; stent dwell times; the number of emergency department (ED) attendances and hospital readmissions; procedure cancellation rates and the number of urinary tract infections.

Results: In total, 162 stents were removed (113 Standard, 34 Isiris™, 15 via strings). Excess dwell time was reduced in both Isiris™ (median 1 day, mean 1.37 days, p = 0.0009) and Strings Groups (median 0.96 days, mean 0.96 days, p = 0.022) compared with the Standard Group (median 8 days, mean 15.34 days).ED attendances and readmissions were reduced by 33.5% and 22% respectively in the Isiris™ Group compared with the Standard Group. There were no ED attendances in the Strings Group. Reductions in length of stay, urine infections and cancellation on the day of procedures were also observed.

Conclusions: The clinical flexibility provided by Isiris™ and 'stents on strings' has objectively improved patient experience and is associated with a reduction in complications as well as increasing diagnostic capacity and cost efficacy.
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http://dx.doi.org/10.5173/ceju.2018.1519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051365PMC
March 2018

When politics meets science: What impact might Brexit have on organ donation and transplantation in the United Kingdom?

Clin Transplant 2018 08 21;32(8):e13299. Epub 2018 Jun 21.

Department of Transplantation, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

Brexit may lead to major political, societal, and financial changes-this has significant implications for a tax revenue funded healthcare system such as the United Kingdom's (UK) National Health Service. The complex relationship between European Union (EU) legislation and clinical practice of organ donation and transplantation is poorly understood. However, it is unclear what impact Brexit may have on organ donation and transplantation in the UK and EU. This work aims to describe the current legislative interactions affecting organ donation and transplantation regulation and governance within the UK and EU. We consider the potential impact of Brexit on the practical aspects of transplantation such organ-sharing networks, logistics, and the provision of health care for transplant patients when traveling to the EU from the UK and vice versa, as well as personnel, and research. Successful organ donation and transplantation practices rely on close collaboration and co-operation across Europe and throughout the United Kingdom. The continuation of such relationships, despite the proposed legislative change, will remain a vital and necessary component for the ongoing success of transplantation programs.
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http://dx.doi.org/10.1111/ctr.13299DOI Listing
August 2018

Links between a biomarker profile, cold ischaemic time and clinical outcome following simultaneous pancreas and kidney transplantation.

Cytokine 2018 05 8;105:8-16. Epub 2018 Feb 8.

Department of Transplantation, Manchester Foundations Hospitals NHS Foundation Trust, Manchester Royal Infirmary, Manchester, United Kingdom.

In sepsis, trauma and major surgery, where an explicit physiological insult leads to a significant systemic inflammatory response, the acute evolution of biomarkers have been delineated. In these settings, Interleukin (IL) -6 and TNF-α are often the first pro-inflammatory markers to rise, stimulating production of acute phase proteins followed by peaks in anti-inflammatory markers. Patients undergoing SPKT as a result of diabetic complications already have an inflammatory phenotype as a result of uraemia and glycaemia. How this inflammatory response is affected further by the trauma of major transplant surgery and how this may impact on graft survival is unknown, despite the recognised pro-inflammatory cytokines' detrimental effects on islet cell function. The aim of the study was to determine the evolution of biomarkers in omentum and serum in the peri-operative period following SPKT. The biochemical findings were correlated to clinical outcomes. Two omental biopsies were taken (at the beginning and end of surgery) and measured for CD68+ and CD206+ antibodies (M1 and M2 macrophages respectively). Serum was measured within the first 72 h post-SPKT for pro- and anti-inflammatory cytokines (IL -6, -10 and TNF-α), inflammatory markers (WCC and CRP) and endocrine markers (insulin, C-peptide, glucagon and resistin). 46 patients were recruited to the study. Levels of M1 (CD68+) and M2 (CD206+) macrophages were significantly raised at the end of surgery compared to the beginning (p = 0.003 and p < 0.001 respectively). Levels of C-peptide, insulin and glucagon were significantly raised 30 min post pancreas perfusion compared to baseline and were also significantly negatively related to prolonged cold ischaemic time (CIT) (p < 0.05). CRP levels correlated significantly with the Post-Operative Morbidity Survey (p < 0.05). The temporal inflammatory marker signature after SPKT is comparable to the pattern observed following other physiological insults. Unique to this study, we find that CIT is significantly related to early pancreatic endocrine function. In addition, this study suggests a predictive value of CRP in peri-operative morbidity following SPKT.
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http://dx.doi.org/10.1016/j.cyto.2018.01.006DOI Listing
May 2018

Pancreas transplantation: the donor's side of the story.

BMJ 2017 08 17;358:j3784. Epub 2017 Aug 17.

Faculty of Medicine, Biology and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

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http://dx.doi.org/10.1136/bmj.j3784DOI Listing
August 2017

Kidney Transplant Recipients Requiring Critical Care Admission Within One Year of Transplant.

Exp Clin Transplant 2017 Feb 2;15(1):40-46. Epub 2016 Dec 2.

From the Department of Transplantation, Central Manchester University Hospitals, United Kingdom.

Objectives: Kidney transplant is the gold standard for treatment of renal failure. With the increasing age of the recipient population, which carries significant comorbidities, and the use of more marginal organs, there is potential for increased critical care admissions. In this study, we investigated the incidence, indications, and outcomes of patients admitted to critical care within 1 year of transplant. We also aimed to identify any precipitating factors or events that may trigger these admissions, as well as establish variables that could affect mortality.

Materials And Methods: We performed a retrospective analysis of kidney transplant recipients admitted to critical care within 1 year after transplant, between January 2009 and December 2013.

Results: Of 1002 kidney transplants, 53 patients (5.3%) were admitted to critical care within 1 year, with patients separated into 2 groups. Group 1 comprised 32 patients (61%) who were admitted immediately postoperatively, mainly from cardiorespiratory derangements with mean stay of 3.7 days (range, 1-34 days) and 0 mortalities. Group 2 comprised 21 patients (39%) who were admitted later in the postoperative period, principally from sepsis-related complications with a mean stay of 18 days (range, 1-101 days). Most patients in group 2 required intensive therapy, including mechanical ventilation and immunosupprression reduction, incurring a hospital mortality rate of 48%. Hemorrhage with reexploration was higher in group 1. Diabetes mellitus, cardiac comorbidity, prolonged stay, nutritional support, nosocomial infections, and multiple organ failure were found at a higher rate in the group 2 patients who died.

Conclusions: The incidence of critical care admissions 1 year after kidney transplant was 5.3%. Most admissions occurred in the early postoperative period, mostly as preemptive measures for cardiorespiratory monitoring and support. This category of admission is potentially preventable with optimization of preoperative treatment. Later admissions were mostly consequential to sepsis-related complications, with patients having a high mortality rate due to multiple organ failure. Clinical management should therefore focus on the prevention of multiple organ failure to improve patient outcomes.
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http://dx.doi.org/10.6002/ect.2015.0356DOI Listing
February 2017
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