Ten Years of Quality Monitoring of Abdominal Organ Procurement in the Netherlands and Its Impact on Transplant Outcome.

In this study, 10 years of procurement quality monitoring data were analyzed to identify potential risk factors associated with procurement-related injury and their association with long-term graft survival. All deceased kidney, liver, and pancreas donors from 2012 to 2022 and their corresponding recipients in the Netherlands were retrospectively included. The incidence of procurement-related injuries and potential risk factors were analyzed. Of all abdominal organs procured, 23% exhibited procurement-related injuries, with a discard rate of 4.0%. In kidneys and livers, 23% of the grafts had procurement-related injury, with 2.5% and 4% of organs with procurement-related injury being discarded, respectively. In pancreas procurement, this was 27%, with a discard rate of 24%. Male donor gender and donor BMI >25 were significant risk factors for procurement-related injury in all three abdominal organs, whereas aberrant vascularization was significant only for the kidney and liver. In the multivariable Cox regression analyses, procurement-related injury was not a significant predictor for graft failure (kidney; HR 0.99, 95% CI 0.75-1.33, p = 0.99, liver; HR 0.92, 95% CI 0.66-1.28, p = 0.61, pancreas: HR 1.16; 95% CI 0.16-8.68, p = 0.88). The findings of this study suggest that transplant surgeons exhibited good decision-making skills in determining the acceptability and repairability of procurement-related injuries.

Applicability and reproducibility of the CPAT-grading system for pancreas allograft thrombosis.

PURPOSE: Although pancreas allograft thrombosis (PAT) incidence has progressively decreased, it remains the most common cause of early graft failure. Currently, there is no consensus on documentation of PAT, which has resulted in a great variability in reporting. The Cambridge Pancreas Allograft Thrombosis (CPAT) grading system has recently been developed for classification of PAT. In this study we aimed to assess the applicability and validate the reproducibility of the CPAT grading system. METHODS: This study is a retrospective cohort study. Selected for this study were all 177 pancreas transplantations performed at our center between January 1 st, 2008 and September 1 st, 2018 were included. RESULTS: A total of 318 Computed Tomography (CT) images was reevaluated according the CPAT system by two local radiologists. Inter-rater agreement expressed in Cohen's kappa was 0.403 for arterial and 0.537 for venous thrombosis. Inter-rater agreement, expressed in the Fleiss' kappa, within clinically relevant thrombosis categories was 0.626 for Grade 2 and 0.781 for Grade 3 venous thrombosis. CONCLUSIONS: Although not perfect, we believe that implementation of the CPAT system would improve current documentation on PAT. However, it is questionable whether identification of a small Grade 1 thrombosis would be relevant in clinical practice. Furthermore, a good quality CT scan, including adequate phasing, is essential to accurately identify potential thrombus and extend after pancreas transplantation.

Pancreas Transplantation With Grafts From Donors Deceased After Circulatory Death: 5 Years Single-Center Experience.

BACKGROUND: Donation after circulatory death (DCD) pancreas transplantation has been shown to be an additional way to deal with donor organ shortages. The results of 5-year DCD pancreas transplantation are presented. METHODS: A retrospective, single-center analysis (2011-2015) was performed to compare the results of donation after brain death (DBD) to DCD pancreas transplantation. RESULTS: During the study period, 104 pancreas transplantations (83 from DBD and 21 from DCD) were performed. Median Pancreas Donor Risk Index (PDRI) was 1.47, (DBD, 1.61 vs DCD, 1.35; P = 0.144). Without the factor DCD, PDRI from DCD donors was significantly lower (DBD, 1.61 vs DCD, 0.97; P < 0.001). Donor age was the only donor-related risk factor associated with pancreas graft survival (Hazard ratio, 1.06; P = 0.037). Postoperative bleeding and kidney delayed graft function occurred more frequently in recipients from DCD (P = 0.006). However, DCD pancreata had a lower incidence of thrombosis. Kidney and pancreas graft survival were equally good in both groups. CONCLUSIONS: Pancreas transplantation from DCD donors yields comparable results to DBD donors when PDRI of DCD is relatively low. Most DCD donors are younger donors with trauma as cause of death. These DCD pancreas grafts may be a better option to cope with increasing organ shortages than exploring the limits with older (and higher PDRI) DBD donors.

Exchange of best practices within the European Union: surgery standardization of abdominal organ retrieval.

Considering the growing organ demand worldwide, it is crucial to optimize organ retrieval and training of surgeons to reduce the risk of injury during the procedure and increase the quality of organs to be transplanted. In the Netherlands, a national complete trajectory from training of surgeons in procurement surgery to the quality assessment of the procured organs was implemented in 2010. This mandatory trajectory comprises training and certification modules: E-learning, training on the job, and a practical session. Thanks to the ACCORD (Achieving Comprehensive Coordination in Organ Donation) Joint Action coordinated by Spain and co-funded under the European Commission Health Programme, 3 twinning activities (led by France) were set to exchange best practices between countries. The Dutch trajectory is being adapted and implemented in Hungary as one of these twinning activities. The E-learning platform was modified, tested by a panel of Hungarian and UK surgeons, and was awarded in July 2013 by the European Accreditation Council for Continuing Medical Education of the European Union of Medical Specialists. As a pilot phase for future national training, 6 Hungarian surgeons from Semmelweis University are being trained; E-learning platform was fulfilled, and practical sessions, training-on-the-job activities, and evaluations of technical skills are ongoing. The first national practical session was recently organized in Budapest, and the new series of nationwide selected candidates completed the E-learning platform before the practical. There is great potential for sharing best practices and for direct transfer of expertise at the European level, and especially to export this standardized training in organ retrieval to other European countries and even broader. The final goal was to not only provide a national training to all countries lacking such a program but also to improve the quality and safety criteria of organs to be transplanted.

Presence of hyperemic islets in human donor-pancreata results in reduced islet isolation yield.

When studying histological characteristics of human donor-pancreata, a remarkably high number of hyperemic islets (HIs) were encountered. The abnormalities in these HIs ranged from single/multiple dilated vessels to hemorrhages extending into the exocrine tissue. We aimed to determine the relevance of the presence of HIs in human donor-pancreata for isolation outcome and to identify donor and procurement factors associated with the occurrence of HIs. The presence of HIs was scored semi-quantitatively (HI-, HI+) in 102 human donor-pancreata. Islet isolation was performed in 40 cases. Donor and procurement factors were retrospectively analyzed in 94 donors. HIs were found in 54.6% of all donor-pancreata. However, only 4.5% of all islets in the affected pancreata was hyperemic. The affected pancreata contained slightly more endocrine tissue, but produced significantly lower yields. When corrected for other factors known to influence isolation outcome, the presence of HIs and endocrine content were the only factors significantly influencing isolation outcome. Prolonged ICU stay and pre-procurement hypertension were associated with the presence of HIs. This study is a first indication that the presence of HIs in human donor-pancreata are associated with reduced isolation outcomes and suggest an impact of the procurement procedure and pre-procurement hemodynamic status of the donor on the islet quality. It is tempting to speculate that this contributes to the generally experienced difficulties in obtaining sufficient amounts of human islets.

Similar liver transplantation survival with selected cardiac death donors and brain death donors.

BACKGROUND: The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive acceptance criteria. METHODS: All adult recipients in the Netherlands in 2001-2006 with full-size OLT from DCD (n = 55) and DBD (n = 471) donors were included. Kaplan-Meier, log rank and Cox regression analyses were used. RESULTS: One- and 3-year patient survival rates were similar for DCD (85 and 80 per cent) and DBD (86.3 and 80.8 per cent) transplants (P = 0.763), as were graft survival rates (74 and 68 per cent versus 80.4 and 74.5 per cent; P = 0.212). The 3-year cumulative percentage of surviving grafts developing non-anastomotic biliary strictures was 31 per cent after DCD and 9.7 per cent after DBD transplantation (P < 0.001). The retransplantation rate was similar overall (P = 0.081), but that for biliary stricture was higher in the DCD group (P < 0.001). Risk factors for 1-year graft loss after DBD OLT were transplant centre, recipient warm ischaemia time and donor with severe head trauma. After DCD OLT they were transplant centre, donor warm ischaemia time and cold ischaemia time. DCD graft was a risk factor for non-anastomotic biliary stricture. CONCLUSION: OLT using controlled DCD grafts and restrictive criteria can result in patient and graft survival rates similar to those of DBD OLT, despite a higher risk of biliary stricture.

Early renal ischemia-reperfusion injury in humans is dominated by IL-6 release from the allograft.

The pathophysiology of ischemia/reperfusion (I/R) injury is complex, and current knowledge of I/R injury in humans is incomplete. In the present study, human living-donor kidney transplantation was used as a highly reproducible model to systematically study various processes potentially involved in early I/R injury. Unique, direct measurements of arteriovenous concentration differences over the kidney revealed massive release of interleukin (IL)-6 in the first 30 minutes of graft reperfusion and a modest release of IL-8. Among the assessed markers of oxidative and nitrosative stress, only 15(S)-8-iso-PGF(2alpha) was released. When assessing cell activation, release of prothrombin factor 1 + 2 indicated thrombocyte activation, whereas there was no release of markers for endothelial activation or neutrophil activation. Common complement activation complex sC5b-9 was not released into the bloodstream, but was released into urine rapidly after reperfusion. To investigate whether IL-6 plays a modulating role in I/R injury, a mouse experiment of renal I/R injury was performed. Neutralizing anti-IL-6 antibody treatment considerably worsened kidney function. In conclusion, this study shows that renal I/R in humans is dominated by local IL-6 release. Neutralization of IL-6 in mice resulted in a significant aggravation of renal I/R injury.

Transfer of ureteral carcinoma in a transplanted kidney presenting by early stenosis of the proximal ureter.

A 71-yr-old male kidney transplant recipient suffered from delayed graft function. Eighty days after transplantation complete obstruction of the proximal ureter was observed, complicated by recurrent urinary tract infections. Two months later, the donor kidney was removed because of infectious complications and inadequate arterial perfusion. Histological examination of the removed graft showed signs of rejection as well as a low-grade papillary urothelial cell carcinoma of donor origin in the ureter. The remaining donor ureter was removed subsequently and showed no further signs of malignancy. Follow-up of the patient until 12 months after surgery did not reveal recurrence of the tumor. This case report is the first to describe accidental transfer of urothelial cell carcinoma in the ureter by transplantation, highlighting the possibility of malignancy when early stenosis is not related to the anastomosis. It again emphasizes the need for precise and cautious screening of organ donors, especially those of higher age.

Isolation of the islets of Langerhans from the human pancreas with magnetic retraction.

Low yield and insufficient purity limit the transplantation of human islets of Langerhans. In the rat, a new technique to isolate the islets of Langerhans was developed by intraarterial infusion of iron particles into the islet capillaries. After digestion the iron-loaded islets were purified with magnetic retraction (MR). In the present study, 10 human pancreata not suitable for clinical use were arterially injected with an iron-oxide suspension. After injection a small piece was used for histological analysis, and the tail was intraductally perfused with collagenase and manually digested. The yield was compared with 11 pancreata processed in the standard way. Nine of 10 pancreata were successfully injected with iron-oxide and digested. After MR, enrichment was achieved but the purity was not more than 50%. Similar results between the 2 groups were obtained regarding digestion times (23 +/- 1.1 vs 22.7 +/- 1.5 minutes) and purification yields (1749 +/- 502.1 vs 2111 +/- 501.8 IE/g, P = .6) for the MR vs control groups, respectively. Histological analysis revealed that 60% to 88% of the islets contained iron aggregations with substantially higher concentrations compared with the exocrine tissue. In conclusion, iron-oxide did not influence the isolation outcome before purification. Islet purification with MR gave enrichment but no pure fractions.

Reuse of auxiliary liver grafts in second recipients with chronic liver disease.

We describe the first cases of reuse of auxiliary liver grafts for orthotopic transplantation in chronic liver disease. A reduced liver graft (segments 2, 3, half of 4) was first transplanted auxiliary for acute liver failure using a new technique. After regeneration of both native liver and graft, the auxiliary graft was removed and immunosuppression discontinued in the first recipients. After informed consent of donors and recipients, both auxiliary grafts were then orthotopically transplanted into second recipients. Both grafts function normally. Reuse of auxiliary grafts may help to reduce the shortage or liver grafts available for transplantation.

A novel technique for auxiliary partial liver transplantation with reno-portal anastomosis and avoidance of the hepatoduodenal ligament.

Auxiliary liver transplantation (ALT) is a treatment for acute liver failure when regeneration of the native liver is possible or for metabolic disorders. In selected cases ALT and orthotopic liver transplantation (OLT) have similar survival when ALT is performed in the orthotopic position (auxiliary partial orthotopic liver transplantation, APOLT). Drawback of ALT with portal vein to portal vein anastomosis is the frequent occurrence of thrombosis, compromising both graft and native liver, and the necessity of a significant resection. To avoid division of portal flow we performed ALT with an end-to-end anastomosis between the graft portal vein and the left renal vein of the recipient (reno-portal ALT, REPALT). The hepatic artery was anastomosed to the aorta using an iliac arterial graft conduit. The bile duct was anastomosed to the stomach. In the two cases presented here excellent immediate graft function occurred with rapid regeneration of the graft and without early vascular complications.

Clinical aspects of small-bowel transplantation.

AIM: To update clinical aspects of small-bowel transplantation. METHODS: Critical review of the literature. RESULTS: The two major functions of the small bowel are absorption of food and protection of the body against ingested pathogens. The highly developed immune system of the bowel, necessary for the latter function, prevented successful small-bowel transplantation during the 1960s and 1970s by provoking early and severe rejection of the graft. The introduction of cyclosporin in the 1980s enabled small-bowel transplantation with a moderate success rate. Further improvement of immunosuppressive regimens, especially the introduction of tacrolimus and aggressive surveillance for and treatment of infections, has resulted in a slow but steady improvement of transplant results during the past decade. At this moment, however, long-term parenteral nutrition is still the first-line treatment of the short-bowel syndrome world-wide because of the excellent results with regard to patient survival. CONCLUSION: Although results of small-bowel transplantation are steadily improving, especially due to better immunosuppressive regimens, long-term parenteral nutrition is still the first-line treatment of short-bowel syndrome.

Capillary electrophoresis of some tetracycline antibiotics coupled with reductive fast cyclic voltammetric detection.

The separation and quantitative performance parameters for tetracycline, chlortetracycline and oxytetracycline antibiotics were investigated by capillary zone electrophoresis coupled with fast cyclic voltammetric detection. Optimization of pH and complexation with a boric acid-sodium tetraborate buffer provided good resolution of all compounds. Detection by electrochemical reduction using fast on-line cyclic voltammetric detection with a Hg-film-microm electrode gave detection limits (2 x peak-to-peak baseline noise) of 7 x 10(-7) mol/l for tetracycline and chlortetracycline, and 1.5 x 10(-6) mol/l for oxytetracycline. The influence of electrode material, potential range and scan rate was examined and discussed. Optimal electrochemical detection was obtained at a Hg-film electrode with a waveform that consisted of an initial constant potential of -0.6 V for 200 ms followed by a cyclic voltammetry (CV) scan at 300 V/s from - 0.6 V to a vertex potential of 1.7 V. The analytical signal was obtained by plotting the integrated values of the CV current from each applied waveform as a function of time. The calibration plot (peak areas) for each separated peak was found to be linear over three-orders of magnitude.

Cyclic voltammetric detection in capillary electrophoresis with application to metal ions.

Fast cyclic voltammetry (CV) was evaluated over sweep rates of 20-1000 V/s at Au disk electrodes (25 and 10 µm) for end-capillary detection in capillary electrophoresis with metal ions as test analytes; some studies were also done with 25-µm Pt disk electrodes. The waveform applied to the electrode consisted of a preconcentration period (55-330 ms) followed by cyclic voltammetry (2-100 ms). Maximum signal-to-noise was obtained with the integrated CV current as the analytical signal, and this was linearly proportional to sweep rate; maximum response was obtained at sweep rates of >100 V/s for 10-µm electrodes and >200 V/s for 25-µm electrodes; sweep rates of >400 V/s caused peak tailing due to trapping of the analyte at the electrode. With this CV detection approach, comigrating analytes could be identified and determined. Reproducibilities for six analytes over the range 1.0 × 10(-)(7)-1.0 × 10(-)(5) mol/L were 2%-5%, and calibration curves were linear, with response factors in the range of 2%-6%. Detection limits (2 × peak-to-peak baseline noise) were in the range of 5 × 10(-)(9)-4 × 10(-)(8) mol/L, which are 1-2 orders of magnitude better than results obtained previously with square-wave pulsed amperometric detection of metal ions.

Control of rate and extent of the proliferative response after partial hepatectomy.

To examine the role of the early changes occurring in the liver within the first hours after a partial hepatectomy and in an attempt to demonstrate the involvement of subsequent regulatory mechanisms, the size of the remnant liver was modified at various times and by different surgical techniques. Male Wistar rats were submitted to a two-thirds "temporary partial hepatectomy" produced by a 3-h occlusion of the pedicle of the anterior lobes protected by local hypothermia. Various indexes of cell proliferation ([3H]thymidine uptake and 5-bromo-2'-deoxyuridine and proliferating cell nuclear antigen labeling) were not increased despite a c-myc expression as high as that observed after a two-thirds partial hepatectomy. The temporary partial hepatectomy and a sham operation induced modifications of the hepatocytes, allowing rapid DNA synthesis after a subsequent two-thirds partial hepatectomy. After this initial nonspecific response, the extent of the regenerative response is determined according to the size of the liver mass present approximately from the 10th to the 18th hour after the initial stimulus. For instance, when a one-third partial hepatectomy was converted into a two-thirds partial hepatectomy at the 10th hour, the DNA synthesis at the 24th hour reached the value observed after a straightforward two-thirds partial hepatectomy. Inversely, the regenerative response was significantly reduced when additional liver lobes were connected to neck vessels between the 14th and the 18th hour after a two-thirds partial hepatectomy. In conclusion, the actual liver mass present during the period corresponding to mid- to late G1 appears to control the magnitude of the proliferative response, which is not the simple consequence of the early changes following a partial hepatectomy.

Effect of sialoadenectomy and epidermal growth factor administration on liver regeneration after partial hepatectomy.

Epidermal growth factor (EGF), a mitogen in vitro for hepatocytes, produces in various cell lines changes similar to those observed very rapidly in hepatocytes after partial hepatectomy (PH). These changes include ion movements, membrane hyperpolarization and proto-oncogene expression. A stimulatory effect of EGF on liver regeneration can therefore tentatively be associated with the events occurring within the first 3 hours after a PH, sometimes referred to as the "priming phase." To assess this hypothesis, we examined in Wistar rats the effect of EGF deprivation produced by sialoadenectomy (SX) performed before or after a PH of 70%. SX at the time of PH significantly decreased the 3H-thymidine uptake in the DNA 24 hours later (147 +/- 14 DPM per microgram of DNA, mean +/- SE) compared with a simple PH (322 +/- 16; P < .01), but also compared with results obtained when PH is combined with a sham sialoadenectomy (SSX) or in rats pair-fed with the sialoadenectomized rats. This incomplete inhibition was confirmed by a decreased rise in thymidine kinase (TK) activity and by reduced proliferating cell nuclear antigen (PCNA) labeling and mitotic indices 30 hours after PH. By contrast, SX did not inhibit the early expression of c-jun and c-fos, or of c-myc, 30 or 120 minutes after PH, respectively. A reduction of DNA synthesis was also obtained when SX was performed 3 hours after PH (127 +/- 15 DPM per microgram of DNA vs. 350 +/- 21 in SSX; P < .001) but not when SX was delayed until the 6th or the 17th hour after PH. It was sufficient to administer EGF (40 microg) from the third to the ninth hour to correct the reduction of [3H]thymidine uptake in rats sialoadenectomized before PH. These results indicate that the diminished EGF availability following SX decreases or at least delays liver regeneration, and that the effect of EGF on liver regeneration does not seem related to the early changes of proto-oncogene expression, but rather to events occuring later, at the time of reported internalization and binding of EGF to its nuclear receptors.