The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation.

The time to arrest donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following donors after circulatory death (DCD) simultaneous pancreas-kidney transplantation. Data were extracted from the UK transplant registry from 2014 to 2022. Predictors of graft loss were evaluated using a Cox proportional hazards model. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. Three-hundred-and-seventy-five DCD simultaneous kidney-pancreas transplant recipients were included. Increasing TTD was not associated with graft survival (adjusted hazard ratio HR 0.98, 95% confidence interval 0.68-1.41, P = .901). Increasing asystolic time worsened graft survival (adjusted hazard ratio 2.51, 95% confidence interval 1.16-5.43, P = .020). Restricted cubic spline modeling revealed a nonlinear relationship between asystolic time and graft survival and no relationship between TTD and graft survival. We found no evidence that TTD impacts pancreas graft survival after DCD simultaneous pancreas-kidney transplantation; however, increasing asystolic time was a significant predictor of graft loss. Procurement teams should attempt to minimize asystolic time to optimize pancreas graft survival rather than focus on the duration of TTD.

Beta-cell death and dysfunction drives hyperglycaemia in organ donors.

BACKGROUND: Donor hyperglycaemia following brain death has been attributed to reversible insulin resistance. However, our islet and pancreas transplant data suggest that other mechanisms may be predominant. We aimed to determine the relationships between donor insulin use and markers of beta-cell death and beta-cell function in pancreas donors after brain death. METHODS: In pancreas donors after brain death, we compared clinical and biochemical data in 'insulin-treated' and 'not insulin-treated donors' (IT vs. not-IT). We measured plasma glucose, C-peptide and levels of circulating unmethylated insulin gene promoter cell-free DNA (INS-cfDNA) and microRNA-375 (miR-375), as measures of beta-cell death. Relationships between markers of beta-cell death and islet isolation outcomes and post-transplant function were also evaluated. RESULTS: Of 92 pancreas donors, 40 (43%) required insulin. Glycaemic control and beta-cell function were significantly poorer in IT donors versus not-IT donors [median (IQR) peak glucose: 8 (7-11) vs. 6 (6-8) mmol/L, p = .016; C-peptide: 3280 (3159-3386) vs. 3195 (2868-3386) pmol/L, p = .046]. IT donors had significantly higher levels of INS-cfDNA [35 (18-52) vs. 30 (8-51) copies/ml, p = .035] and miR-375 [1.050 (0.19-1.95) vs. 0.73 (0.32-1.10) copies/nl, p = .05]. Circulating donor miR-375 was highly predictive of recipient islet graft failure at 3 months [adjusted receiver operator curve (SE) = 0.813 (0.149)]. CONCLUSIONS: In pancreas donors, hyperglycaemia requiring IT is strongly associated with beta-cell death. This provides an explanation for the relationship of donor IT with post-transplant beta-cell dysfunction in transplant recipients.

Kidney Transplantation From Donors With Acute Kidney Injury: Are the Concerns Justified? A Systematic Review and Meta-Analysis.

Renal transplantation improves quality of life and prolongs survival in patients with end-stage kidney disease, although challenges exist due to the paucity of suitable donor organs. This has been addressed by expanding the donor pool to include AKI kidneys. We aimed to establish whether transplanting such kidneys had a detrimental effect on graft outcome. The primary aim was to define early outcomes: delayed graft function (DGF) and primary non-function (PNF). The secondary aims were to define the relationship to acute rejection, allograft survival, eGFR and length of hospital stay (LOS). A systematic literature review and meta-analysis was conducted on the studies reporting the above outcomes from PubMed, Embase, and Cochrane Library databases. This analysis included 30 studies. There is a higher risk of DGF in the AKI group (OR = 2.20, p < 0.00001). There is no difference in the risk for PNF (OR 0.99, p = 0.98), acute rejection (OR 1.29, p = 0.08), eGFR decline (p = 0.05) and prolonged LOS (p = 0.11). The odds of allograft survival are similar (OR 0.95, p = 0.54). Transplanting kidneys from donors with AKI can lead to satisfactory outcomes. This is an underutilised resource which can address organ demand.

Enhanced recovery after surgery recommendations for renal transplantation: guidelines.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) protocols are now widely practiced in major surgery, improving postsurgical outcomes. Uptake of these programmes have been slow in kidney transplantation due to challenges in evaluating their safety and efficacy in this high-risk cohort. To date, there are no unified guidance and protocols specific to ERAS in kidney transplantation surgery. This paper aims to summarise current evidence in the literature and develop ERAS protocol recommendations for kidney transplantation recipients. METHODS: PubMed, Cochrane, Embase and Medline databases were screened for studies relevant to ERAS protocols in kidney transplantation, up to August 2021. A secondary search was repeated for each ERAS recommendation to explore the specific evidence base available for each section of the protocol. Randomised controlled trials, case-control and cohort studies were included. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework was used to evaluate the quality of evidence available and recommendations. RESULTS: We identified six eligible studies with a total of 1225 participants. All studies found a reduction in length of hospital stay without affecting readmission rates. The evidence behind specific pre-operative, intra-operative and post-operative interventions included in current ERAS protocols are reviewed and discussed. CONCLUSION: Compared to other surgical specialties, the evidence base for ERAS in kidney transplantation remains lacking, with further room for research and development. However, significant improvements to patient outcomes are already possible with application of the currently available evidence. This has shown that ERAS in kidney transplantation surgery is safe and feasible, with improved postoperative outcomes.

Kidney Transplantation From Hepatitis-C Viraemic Donors:Considerations for Practice in the United Kingdom.

Background: Donor hepatitis-C (HCV) infection has historically represented a barrier to kidney transplantation (KT). However, direct-acting antiviral (DAA) medications have revolutionised treatment of chronic HCV infection. Recent American studies have demonstrated that DAA regimes can be used safely peri-operatively in KT to mitigate HCV transmission risk. Methods: To formulate this narrative review, a comprehensive literature search was performed to analyse results of existing clinical trials examining KT from HCV-positive donors to HCV-negative recipients with peri-operative DAA regimes. Results: 13 studies were reviewed (11 single centre, four retrospective). Outcomes for 315 recipients were available across these studies. A sustained virological response at 12 weeks (SVR12) of 100% was achieved in 11 studies. One study employed an ultra-short DAA regime and achieved an SVR12 of 98%, while another achieved SVR12 of 96% due to treatment of a missed mixed genotype. Conclusion: HCV+ KT is safe and may allow increased utilisation of organs for transplantation from HCV+ donors, who often have other favourable characteristics for successful donation. Findings from US clinical trials can be applied to the United Kingdom transplant framework to improve organ utilisation as suggested by the NHSBT vision strategy "Organ Donation and Transplantation 2030: meeting the need".

Donor Autonomy and Self-Sacrifice in Living Organ Donation: An Ethical Legal and Psychological Aspects of Transplantation (ELPAT) View.

Clinical teams understandably wish to minimise risks to living kidney donors undergoing surgery, but are often faced with uncertainty about the extent of risk, or donors who wish to proceed despite those risks. Here we explore how these difficult decisions may be approached and consider the conflicts between autonomy and paternalism, the place of self-sacrifice and consideration of risks and benefits. Donor autonomy should be considered as in the context of the depth and strength of feeling, understanding risk and competing influences. Discussion of risks could be improved by using absolute risk, supra-regional MDMs and including the risks to the clinical team as well as the donor. The psychological effects on the donor of poor outcomes for the untransplanted recipient should also be taken into account. There is a lack of detailed data on the risks to the donor who has significant co-morbidities.

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

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.

Laterality in laparoscopic hand assisted donor nephrectomy - Does it matter anymore? Outcomes of a large retrospective series.

This retrospective study was performed to analyse if laterality of the retrieved living donor kidney had any effect on donor and recipient outcomes after hand assisted laparoscopic donor nephrectomy (HALDN). 739 donors who underwent HALDN between January 2006 and January 2018 at a large tertiary transplant centre in the United Kingdom were included. Donor outcomes in individuals undergoing right versus left HALDN were compared with respect to conversion rates, morbidity, warm and cold ischaemia times and recipient failure rates, vascular and ureteric complications. 604 (81.7%) underwent left HALDN and 135 (18.3%) underwent right HALDN, mean age was 47.1 years and 46.8 years respectively with comparable gender distribution. The operative time was shorter for the left side (p = 0.003) and improved during the study for the left but not the right side. In recipients who received left kidneys there were more early technical failures observed (8 versus 1) though not statistically significant. Most centres prefer performing a left nephrectomy and recipient surgeons prefer a left kidney for transplantation primarily because of having a longer vein. This large study provides reassurance that right HALDN nephrectomy is a safe procedure with similar outcomes to left HALDN.

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

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.

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

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.

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.

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.

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

Background. 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. Methods. 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. Results. One hundred and fifty ureteric stents were removed in transplant recipients (mean age 50.2 years, SD ± 15.2; 61.3% male). 91.3% (n = 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. Conclusion. 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.

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

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.

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

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 (ß [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.

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

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.

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

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.

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

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.

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

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.

Insulin therapy in organ donation and transplantation.

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.

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

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.