Background Pancreas Transplantation (PT) provides optimal treatment for patients with severe complicated Type 1 Diabetes Mellitus (T1DM). Restoration of beta-cell mass allows return to euglycaemia and insulin independence. We aimed to examine its impact on the secondary complications associated with severe T1DM including diabetic eye disease, neuropathy and cardiovascular disease. Methods A database search using MedLINE to identify publications to April 2023 was conducted. Searches were performed using MeSH terms ‘Pancreas Transplantation’ AND ‘Diabetes Mellitus, Type 1’ ‘Diabetic Retinopathy’ OR ‘Heart Disease’ OR ‘Cardiovascular Diseases’ OR ‘Peripheral Vascular Disease’ OR “Amputation’ OR ‘Neuropathy.” Results All articles were retrospective with 51.1 % (n = 23) case control studies and 48.9 % (n = 22) cohort studies. 82.2 % (n = 37) examined simultaneous pancreas and kidney (SPK) transplantation and 17.8 % (n = 8) analysed pancreas transplant alone (PTA). Heterogenous outcomes metrics were employed. 15 studies examined diabetic retinopathy (DR) with 53.3 % (n = 8) demonstrated improvements after PT, while the remainder (n = 7) exhibited stabilisation. 16 studies assessed neuropathy and 87.5 % (n = 14) demonstrated beneficial effects of PT on nerve conduction studies, vibration perception threshold or corneal confocal microscopy. There was a positive effect on cardiovascular disease by reduction in the incidence of cardiac events, improvement in metabolic profile and increased left ventricular ejection fraction. 14 studies examined cardiovascular disease (71.4 % (n = 10) improvement; 14.2 % (n = 2) stabilisation; 14.2 % (n = 2) progression). Conclusion SPK and PTA have beneficial effects in ameliorating or stabilising diabetes complications. Future work should seek to reduce heterogeneity of outcome metrics assessing T1DM complication profile to facilitate robust comparison of beta-cell replacement interventions.
This systematic review assesses the evidence on treatment options available for glycaemic control after pancreas transplantation (PT) failure (further PT (PAP), islet transplantation (IAP) or best medical therapy (BMTAP)). A systematic literature review using PRISMA methodology analysed MedLINE, EMBASE and Cochrane databases from 2000-2024. Employed MeSH terms included (‘Islet transplantation’ AND ‘pancreas transplantation’ AND ‘type 1 diabetes’ AND ‘graft failure’) OR ‘Pancreas retransplantation’ OR (‘Type 1 diabetes’ AND (insulin pump OR diabetes technology OR insulin therapy OR automated insulin delivery) AND graft failure). Across the 16 studies included, 1393 patients received PAP, 14 patients received IAP and six patients received BMTAP. Mean age of recipients was 38.3, 48.6 and 43.0 years respectively. 31.4% of PAP recipients experienced Clavien-Dindo grade >II complications, with 1-Year graft survival of 37.2-100%. IAP induced a decrease in HbA1c by 8-32 mmol/mol across 3 studies with mean daily exogenous insulin between 0.21-0.37 units/kg. Mean daily insulin dose with BMTAP reduced from 0.53-0.41 units/kg. There was no difference in frequency of severe hypoglycaemic episodes (SHE) before or after commencement of BMTAP. One patient experienced SHE after IAP. PAP and IAP preserved renal function more than standard insulin regimes. PAP provides excellent outcomes but is associated with morbidity and early graft loss. IAP offers improvements in glycaemic control, typically with supplemental exogenous insulin, suitable for recipients with reduced cardiorespiratory reserve. BMTAP with diabetes technology has limited data in setting of severe complicated T1DM or PT failure but may become an important viable alternative or adjunct.
Abstract Aim The risk of urological complications following kidney transplantation is reduced by the intraoperative insertion of ureteric stents. Transplant ureteric stent removal (TUSR) has traditionally been performed in theatre using flexible cystoscopy. Isiris® is a single-use flexible cystoscope. The aim is to analyse the acceptability, efficacy, and cost-effectiveness of Isiris®, for TUSR in a ward/outpatient setting. Method A retrospective analysis of a contemporaneously maintained database at a high-volume kidney transplant centre from January 2021 to June 2022. Data collected included clinico-demographic, operative and stent removal details including time to removal (gold-standard within 6 weeks) and refusal rates. A cost analysis was also performed based on equipment costs and NHS tariffs. TUSR was performed using Isiris® in outpatient ANP-led clinics or on wards by surgical middle grades or ANPs. Results 345 patients were included in analysis with a median age of 54 (19-81). 99.13% were single ureteric anastamoses with 348 stents removed in total. The M:F ratio was 1.32:1. 98.85% of stents were removed using Isiris®, with a 1.15% refusal rate. 86.34% (n=297) were removed in clinic. Median dwell-time was 34 days, IQR 17.25 (25.75-43). 73.84% of stent removal was within 6 weeks. There were savings of £545.00 per stent removal, including expenses for failed Isiris TUSR, with overall savings of £154,021.20 and 86 theatre sessions freed for other activity. Conclusions Isiris® was acceptable and effective for TUSR. Savings were demonstrated compared to TUSR in theatre. Outpatient/ward TUSR reduces demand for theatre time, freeing theatres for other elective activities.
Abstract Aim Vascular anastomosis is an important but complex skill requiring mastery by trainees across multiple specialities, with significant risk of suboptimal outcomes. Simulation allows multiple repetitions of a procedure within controlled environment, allowing training without accompanying patient risk. Current simulation courses on vascular anastomosis are expensive and inaccessible to several junior trainees. A low-cost scaffold was developed for vascular anastomosis training and aimed to assess trainee feedback on utility and acceptability. Method The kit was built using following: Six 27 x 0.9 cm latex balloons, Ferrero Rocher chocolate box, Polypropylene 6.0 surgical sutures, Castroviejo needle holder and Forceps. Sharp scissors were used to make openings in the chocolate box, the balloons were then passed through. The kit’s utility was assessed via trainee feedback (N=16, ranked 1-5 where 1 was Unsatisfactory and 5 was Excellent). Results Trainees were able to perform various types of anastomoses: end-to-end, end-to-side, and patching, using our model. The resistance to needle passage through latex balloons was found to closely resemble that of real arteries and veins. Median rating of different categories in trainee feedback were as followed: Improved understanding 4, Helped practice 5, Realistic 4, Appropriateness for learning 4 and Affordability 5, ranging between 3 and 5. Conclusions Improved skills lead to better outcomes in surgical practice. Steps should be taken to make simulation more accessible. Low-cost models help reduce financial impact on trainees and are suitable for a wide range of institutions, including those with limited resources. Subsequent research should assess the effectiveness of this model across various contexts.
Abstract Background Pancreas transplantation (PT) provides diabetic cure for patients with complicated diabetes mellitus. However, there is a paucity of suitable donor organs to fulfil requirements resulting in deaths on the waiting list. Organs from otherwise suitable hepatitis C virus positive (HCV+) donors alongside direct-acting antiviral agents (DAAs) have been used in kidney and liver transplants in small trials. We aimed to review this strategy in PT. Method A literature search was conducted on OVID MedLINE, PubMed and EMBASE to evaluate evidence on the use of HCV+ organ donors for PT in HCV- recipients alongside DAA therapy. Results Database analysis produced 5 articles (4 single centre retrospective, 1 case report). This included a total of 65 patients, 15 of which received PT. Two studies examined multiple organ transplants whilst 3 evaluated PT alone. Three studies employed prophylactic perioperative therapy, while 2 examined treatment post-transplantation. 100% of patients achieved a sustained virological response (SVR) at 12 weeks across all 5 studies. There were no episodes of acute rejection or complications directly associated with DAA therapy or HCV infection. HCV transmission occurred in only 1 of 15 patients, which was successfully treated. Pancreatic graft function and outcome after 7-12 months was good. Conclusions The use of DAA therapy is safe and effective for HCV+ donors to HCV- transplant in early reported studies. This approach could facilitate the successful utilisation of HCV+ organs for transplantation thereby minimising impact on supply and demand disparities. Pancreas transplantation specific studies are required to further analyse outcomes.
Abstract Aim Simultaneous Islet and Kidney (SIK) transplantation aims to improve glycemic control and renal function by combining an islet transplant with a renal allograft for patients with Type 1 Diabetes Mellitus (T1DM) and renal failure. This provides diabetic improvement and removal from dialysis burden, with reduced peri-operative risk compared to solid organ simultaneous pancreas and kidney transplantation. We aimed to evaluate the outcomes of the United Kingdom’s initial cohort. Method A retrospective analysis of SIK recipients was performed between 03/2017 and 04/2023 at our hospital. Results 22 SIK were performed (72.7% donors after brain death). The mean recipient age was 56 with 54.5% female. The median diabetes duration was 42 years (IQR 22) with median post-SIK follow-up of 361 days (IQR 783). There was a median 1 infusion per recipient (median IQR 1) with median islet equivalence (IEQ) of 323,500 IEQ (IQR 141,250). HbA1c and exogenous insulin requirements were significantly lower after transplant (HbA1c: 62.7 vs 51.6mmol/mol, p<0.001; IU: 40 vs 23 units/day, p<0.001) while C-peptide significantly increased (15.9 vs 535.8pmol/l, p<0.001). Hypoglycaemic episodes/patient/year reduced (7 pre-transplant, vs 1.5 post-transplant). Median islet graft survival was 4.9 years. lgls functional classification at the end of follow-up was satisfactory (7 Optimal, 1 Good, 10 Marginal and 4 Failure). eGFR significantly increased post-SIK (15.4 vs 49mL/min/1.73m2, p<0.001). Conclusions SIK ameliorates renal failure whilst improving glycaemic control with a satisfactory complication profile. Larger and longer cohort analysis is required to fully understand the benefits of SIK for patients with complicated T1DM.
Abstract Introduction A quarter of UK SPK transplants are from Deceased Cardiac Donors(DCD), with an increasing number recovered following in-situ normothermic regional perfusion(NRP). The aim of this study was to review the UK experience of SPK transplantation following NRP in DCD. Methods Data were collected on all first DCD SPKTs(n=360) performed during 2013–2021 from the UK Transplant Registry. Non-NRP DCD SPK were compared to NRP DCD SPKs. Kaplan Meier plots and cox regression analyses were performed. Results Some 198 pancreas were offered from NRP donors with 83 being retrieved. The majority of SPK grafts were from nonNRP donors n=324(90.0%) with n=36(10.0%) from NRP donors. The median cold ischaemic time (CIT) from NRP donors (9.7 hours) was significantly less than nonNRP donors (10.2 hours) (p=0.013). For all other parameters, donors were well matched. Recipients who received a graft from an NRP donor were also well matched with the recipients who received a graft from a nonNRP donor. Univariate analysis showed no statistically significant difference in one-year pancreas graft (NRP 97.2%, non-NRP 89.2%, p=0.145), kidney graft (NRP 100%, nonNRP 95.9%, p=0.221) or patient survival (NRP 100%, nonNRP 98.3%, p=0.442) despite an increasing trend in favour of NRP SPK. Conclusions This is the largest reported analysis of NRP for SPK transplants to date. NRP has previously been shown to be beneficial for liver transplants. Despite some concerns that NRP may preferentially benefit the liver at the expense of other organs our study has shown no adverse effects. Larger studies are needed to evaluate whether NRP improves graft utilisation rates for SPK.
Abstract Aim Pancreas transplantation (PT) is performed for restoration of endocrine function in type 1 diabetes mellitus with amelioration of diabetic complications. However, PT can have serious complications requiring salvage pancreatectomy and surgical approaches should be carefully considered. Anastomoses to jejunum or ileum are most often employed. We compare outcomes between these techniques. Method A retrospective analysis was performed on simultaneous pancreas and kidney transplants (SPK) at Manchester University Hospitals NHS Foundation Trust between 2013 and 2015. Follow up was completed until 2020. Results 86 SPK were performed. 59.2% were male with mean age of 41.5yo (SD±8.4). 72.4% (n = 55) were donors after brain death and 98.7% (n = 75) were receiving first PT. 43 SPK were performed with ileal anastomosis, 33 jejunal. There were no significant differences in demographics of recipients, donors, immunosuppression regimens, overall patient and graft survival and frequency of GI complications. Length of hospital stay was higher with ileal anastomosis (median 14 v 19 days, p<0.05), as was cold ischaemic time (median 8:48 v 9:31 hours, p<0.05). Three patients required salvage pancreatectomy and loop ileostomy formation with multi-organ support and prolonged ITU stay. Conclusions Long term outcomes between groups were comparable in this cohort. Catastrophic complications occur in the minority requiring salvage surgery. Here more occurred with ileal anastomosis, but this approach allows graft pancreatectomy and formation of loop ileostomy, avoiding a more proximal stoma in a clinically unstable patient. Further powered studies are required to rigorously examine the impact of enteric anastomosis site.
Introduction Outcomes following pancreas transplantation are suboptimal and better donor selection is required to improve this. Vasoactive drugs (VaD) are commonly used to correct the abnormal haemodynamics of organ donors in intensive care units. VaDs can differentially affect insulin secretion positively (dobutamine) or negatively (noradrenaline). The hypothesis was that some VaDs might induce beta-cell stress or rest and therefore impact pancreas transplant outcomes. The aim of the study was to assess relationships between VaD use and pancreas transplant graft survival. Methods Data from the UK Transplant Registry on all pancreas transplants performed between 2004 and 2016 with complete follow-up data were included. Univariable- and multivariable-adjusted Cox regression analyses determined risks of graft failure associated with VaD use. Results In 2,183 pancreas transplants, VaDs were used in the following numbers of donors: dobutamine 76 (3.5%), dopamine 84 (3.8%), adrenaline 161 (7.4%), noradrenaline 1,589 (72.8%) and vasopressin 1,219 (55.8%). In multivariable models, adjusted for covariates and the co-administration of other VaDs, noradrenaline use (vs non-use) was a strong predictor of better graft survival (hazard ratio [95% confidence interval] 0.77 [0.64-0.94], p = 0.01). Conclusions Noradrenaline use was associated with better graft survival in models adjusted for donor and recipient variables - this may be related to inhibition of pancreatic insulin secretion initiating pancreatic beta-cell 'rest'. Further research is required to replicate these findings and establish whether relationships are causal. Identification of alternative methods of inducing beta-cell rest could be valuable in improving graft outcomes.
Introduction: Patients with complicated type 1 diabetes mellitus (T1DM) who were eligible for islet cell transplant (ICT) already have a significant comorbidity burden prior to transplant with a high mortality risk. Technological advancements, including continuous glucose monitoring (CGM) and insulin pump technology, minimise life threatening hypoglycemia and optimise secondary cardiovascular event prevention. Methods: A retrospective study of patients with T1DM who had been referred for ICT or simultaneous islet kidney transplant (SIK) at Manchester Royal Infirmary was conducted to evaluate differences in pre-transplant diabetes management between those patients who have successfully been transplanted compared to those who died whilst awaiting for a transplant or during the assessment period. Results: Twenty patients who had ICT were compared to thirty patients who died whilst waiting for transplant or during the assessment period. Data was tested for normality using the Shapiro-Wilks normality test. Parametric (T-test), Non-parametric (Mann-Whitney) or Chi Sq were performed to determine differences between groups with P<0.05 determined to be significant. There were no significant differences between the group who were transplanted compared to those who died in mean age (55.1±3.0 vs. 55.8±2.0 years, P=0.8), sex (55% vs. 37% female, p=0.16), ethnicity (all white), T1DM duration (36.1±2.3 vs. 33.8±2.0 years, P=0.5), weight (78.1±3.5 vs. 70.3±2.7 kg, P=0.2) HbA1c (63.4±3.2 vs 62.8±1.7 mmol/mol, P=0.9) or daily insulin dose (37.1±2.3 vs. 40.2±2.8 units, P=0.7). There were no significant differences in the prevalence of end stage renal failure, diabetic retinopathy or cardiovascular disease. Nineteen patients in the transplanted group had been using CGM with an average duration of use of 56 months, with only one patient using finger-prick testing. In the cohort that died prior to transplantation, 10 out of 30 patients had been using CGM (mean duration:20 months). The percentage using CGM in the transplanted group was significantly higher (95% vs 33.3 %, P<0.001). In the group who died mean time on the list was 41 months in those on CGM compared to 26 months in those without. Seven out of 20 patients in the transplanted group were managed with insulin pumps while 5 out of 30 patients in the group that died were managed using insulin pumps. Whilst 7 patients’ hypoglycemic awareness improved with CGM/insulin pump in the transplanted group, there was only one patient whose hypoglycemic awareness improved in the group that died prior to transplantation. Conclusion: The utilization of CGM and insulin pump therapy was lower in the group who died prior to having a transplant. NICE recommends use of CGM for all patients with T1DM. These results support the use of technology as for the management of this high-risk group of patients to improve the likelihood of survival to transplantation. Further detailed analysis of the CGM data in these groups is warranted.
Abstract Aims Encapsulating peritoneal sclerosis (EPS) is a rare phenomenon characterised by encasement of the bowel by a thickened peritoneum due to prolonged peritoneal dialysis exposure. We are an international referral centre, typically managing cases with a planned open abdomen (OAM) and scheduled relook after 24–48 hours. We compare outcomes for those patients whose OAM was with simple packing (betadine-soaked-gauze) with negative pressure therapy providing temporary abdominal closure (TAC). Methods A retrospective review of a contemporaneous database of patients who underwent surgery for EPS between 2010–2020 was performed. Primary endpoints were time to definitive closure and closure method (primary fascial closure vs. bridged biologic mesh closure vs. failure to close fascia). Secondary endpoints included comparison of stoma formation, bowel resection, fistulation rate, enterotomy formation, re-operation post closure, and wound infection. Results 99 patients had OAM (56 static packing; 43 TAC.) Patients with TAC were significantly more likely to undergo primary closure of fascia when compared to those patients managed with static packing, (63% vs 13%, p<0.0001, Chi Sq). The TAC group required fewer theatre episodes (n=2.27 vs. 4.78, p<0.0001, t-test) and time in days to achieve closure (n=2.78 vs n=4.68, p<0.005, Chi Sq), with less failure to close episodes and returns to theatre 30 days post closure. Conclusion This study provides definitive evidence of TAC efficacy for fascial closure following OAM. This provides definitive benefit over traditional open abdominal methods. It may provide benefit in definitive open abdominal management in other areas (sepsis and trauma) and requires further study.
Abstract Aim We aimed to demonstrate the relative safety profile of an established non-crosslinked porcine acellular dermal matrix (ADM) during abdominal wall reconstruction. Material & Methods Individual real-world safety data on specific mesh products are often lacking. With recent media scrutiny over the use of mesh, we sought to quantify outcomes and demonstrate the safety of a specific ADM (reference 1). A retrospective casenote-based outcome analysis was performed on patients who underwent mesh augmentation during abdominal wall reconstruction from two NHS institutions. Both elective and emergency patients were included from January 2018 to December 2021. Results Fifty-five patients were included in the study across two NHS specialist hernia centres. We identified a mean wound infection rate of 14.2% (range 2–22%) with a median follow up of 9 months (range 3–18 months). Hernia recurrence rate was 10.4% (range 5–22%). We found 7 patients (12%) developed a seroma, 1 of whom required seroma aspiration. Only 4 patients (7%) had post-operative dehiscence requiring further intervention, all of whom had Ventral Hernia Working Group (VHWG) Grade 3 or 4 wounds pre-operatively. Conclusions Our data supports the continued use of a widely available ADM for abdominal wall reconstruction in both elective and emergency cases, highlighting its positive relative safety profile.
Abstract Aim There is currently no established UK database establishing reliable outcome data for surgical repair of incisional herniae (IH). Their heterogeneity (variability in size, patient comorbidity, and multiple repair techniques) has resulted in no surgical management or outcome reporting consensus. This study aims to utilise national trainee led research collaboratives to perform a multi-centre, observational, prospective study to assess variation in IH defects (by utilising pre-defined criteria from The European Hernia Society (EHS) classification for IH and a Modified Ventral Hernia Working Group) and their subsequent operative management. This study will yield valuable, standardised data on variation in practice and outcomes (complications and 3 and 12-months follow-up) to provide a platform for expanding IH research. Materials and Methods All NHS hospitals in England undertaking elective IH repair will be eligible for inclusion. Dissemination of and recruitment to the study will be driven by regional research collaborative networks. This study will include all elective adult IH repairs with. Data will be collected and managed using REDCap electronic data capture tool. There will be three distinct phases comprising; The study is currently unfunded. Funds are sought to obtain NHS Trust sponsorship and proceed to phase 3 of the study.
Pancreas transplantation (PT) allows improved glycaemic control for patients with complicated type 1 diabetes mellitus and is most commonly performed simultaneously with a renal transplant. Imaging modalities are critical for the assessment of pancreatic graft dysfunction, as clinical assessment and hyperglycaemia lack robust sensitivity for the transplant clinician. Biopsy represents the most conclusive standard of PT graft assessment but is challenging due to its invasive nature and the potential morbidity associated with the procedure. Innovative imaging technologies offer the opportunity to apply these modalities to improve PT outcomes while using non-invasive technologies to provide a diagnostic sensitivity that traditionally only biopsies can provide. Early graft dysfunction has traditionally been investigated with Computed tomography (CT) and ultrasound (US) scans. We explore adjuncts to these modalities including the application of contrast enhanced ultrasound (CEUS) for routine post-operative graft assessment to inform post-operative treatment strategies. There is currently a dearth of imaging modalities to reliably monitor long term graft function, but the use of innovative functional imaging techniques and how they can be applied to PT is discussed. Perfusion CT and glucose stimulated magnetic resonance imaging (MRI) to detect whole organ function are examined. In addition, early phase developments in beta-cell specific imaging methods to quantify beta-cell mass longitudinally are described. The clinical applications of such tools including Mn2+-enhanced MR and GLP-1R targeted PET/CT are reviewed and may demonstrate opportunities to provide the transplant clinician with greater information to support improved patient care.
Abstract Introduction WHO declared a pandemic of COVID-19 in March 2020. This study analyses the impact of COVID-19 on beta-cell replacement therapy in the UK. Methods Pancreas and islet donation and transplant activity in the period March 2020/2021 was compared with the same period the previous year. Results 2,180 patients had a functioning graft during March 2020/2021. 5.8%(n=126) tested positive for COVID-19 and two died (1%). In this period there was a 43% reduction in solid organ donors n=1,615, compared with the previous year, n=2,840. Of the 625 solid organ donors with a pancreas offered, 32% had the pancreas retrieved compared with 51% the previous period. 97 whole pancreas and islet transplants were performed in the UK down 54% from the prior period. Of the 84 pancreas transplant recipients; four tested positive for COVID-19 but none died, and two grafts failed within the first week from vascular thrombosis (neither were COVID-19 positive). Of the 13 SIK and islet alone transplant recipients, two tested positive for COVID-19 but neither died. Of these SIK transplants, one is known to have failed within a month and this is equivalent to that seen in the previous time period. To our knowledge, no patient receiving beta cell replacement therapy died of COVID during the first year of the pandemic despite immunosuppression. Conclusion In the UK, pancreas, and islet transplantation have continued during the pandemic at a lower rate. Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior. Take-home message Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior.
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) x 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.