Effective and safe implementation of robot-assisted donor nephrectomy by experienced laparoscopic surgeons.

BACKGROUND: In June 2021, the first robot-assisted donor nephrectomy (RADN) was performed at the Leiden University Medical Center (LUMC), the Netherlands. The goal of this study was to investigate whether this procedure has been implemented safely and efficiently. METHODS: RADN was retrospectively compared to laparoscopic donor nephrectomy (LDN) performed during the same time period (June 2021 until November 2022). Patients were assigned to RADN depending on the availability of the da Vinci robot and surgical team. The studied endpoints were postoperative complications, operative time, estimated blood loss, warm ischemic time (WIT), and postoperative pain experience. For analysis, the Student's t-test and Chi-squared test were used for, respectively, continuous and categorical data. RESULTS: Forty RADN were compared to 63 LDN. Total insufflation time was significantly longer in RADN compared to LDN (188 min (169-214) versus 172 min (144-194); p = 0.02). Additionally, WIT was also found to be significantly higher in the robot-assisted group (04:54 min vs. 04:07 min; p < 0.01). No statistical differences were found in postoperative outcomes (eGFR of the recipient at 3-month follow-up, RADN 54.08 mL/min ±18.79 vs. LDN 56.41 mL/min ±16.82; p = 0.52), pain experience, and complication rate. CONCLUSION: RADN was safely and efficiently implemented at the LUMC. It's results were not inferior to laparoscopic donor nephrectomy. Operative time and warm ischemic times were longer in RADN. This may relate to a learning curve effect. No clinically relevant effect on postoperative outcomes was observed.

Quality assessment of donor liver procurement surgery using an unadjusted CUSUM prediction model. A practical nationwide evaluation.

BACKGROUND: The aim of this study was to analyze the value of the unadjusted CUSUM graph of liver surgical injury and discard rates in organ procurement in the Netherlands. METHODS: Unadjusted CUSUM graphs were plotted for surgical injury (C event) and discard rate (C2 event) from procured livers accepted for transplantation for each local procurement team compared with the total national cohort. The average incidence for each outcome was used as benchmark based on procurement quality forms (Sep 2010-Oct 2018). The data from the five Dutch procuring teams were blind-coded. RESULTS: The C and C2 event rate were 17% and 1.9%, respectively (n = 1265). A total of 12 CUSUM charts were plotted for the national cohort and the five local teams. National CUSUM charts showed an overlapping "alarm signal." This overlapping signal for both C and C2, albeit a different time period, was only found in one local team. The other CUSUM alarm signal went off for two separate local teams, but only for C events or C2 events respectively, and at different points in time. The other remaining CUSUM charts showed no alarm signaling. CONCLUSION: The unadjusted CUSUM chart is a simple and effective monitoring tool in following performance quality of organ procurement for liver transplantation. Both national and local recorded CUSUMs are useful to see the implication of national and local effects on organ procurement injury. Both procurement injury and organ discard are equally important in this analysis and need to be separately CUSUM charted.

Liver Injury and Acute Liver Failure After Bariatric Surgery: An Overview of Potential Injury Mechanisms.

The obesity epidemic has caused a surge in the use of bariatric surgery. Although surgery-induced weight loss is an effective treatment of nonalcoholic fatty liver disease, it may precipitate severe hepatic complications under certain circumstances. Acute liver injury (ALI) and acute liver failure (ALF) following bariatric surgery have been reported in several case series. Although rare, ALI and ALF tend to emerge several months after bariatric surgery. If so, it can result in prolonged hospitalization, may necessitate liver transplantation, and in some cases prove fatal. However, little is known about the risk factors for developing ALI or ALF after bariatric surgery and the mechanisms of liver damage in this context are poorly defined. This review provides an account of the available data on ALI and ALF caused by bariatric surgery, with emphasis on potential injury mechanisms and the outcomes of liver transplantation for ALF after bariatric surgery.

Efficacy of profound versus moderate neuromuscular blockade in enhancing postoperative recovery after laparoscopic donor nephrectomy: A randomised controlled trial.

BACKGROUND: Profound neuromuscular blockade (NMB) during anaesthesia has been shown to reduce postoperative pain scores, when compared with a moderate block. We hypothesised that profound NMB during laparoscopic donor nephrectomy (LDN) could also improve the early quality of recovery after surgery. OBJECTIVES: To compare the effectiveness of profound versus moderate NMB during LDN in enhancing postoperative recovery. DESIGN: A phase IV, double-blinded, randomised controlled trial. SETTING: Multicentre trial, from November 2016 to December 2017. PATIENTS: A total of 101 living kidney donors scheduled for LDN were enrolled, and 96 patients were included in the analyses. INTERVENTIONS: Patients were randomised to receive profound (posttetanic count 1 to 3) or moderate (train-of-four count 1 to 3) neuromuscular block. MAIN OUTCOME MEASURES: The primary outcome was the early quality of recovery at postoperative day 1, measured by the Quality of Recovery-40 Questionnaire. Secondary outcomes were adverse events, postoperative pain, analgesic consumption and length-of-stay. RESULTS: The intention-to-treat analysis did not show a difference with regard to the quality of recovery, pain scores, analgesic consumption and length-of-stay. Less intra-operative adverse events occurred in patients allocated to profound NMB (1/48 versus 6/48). Five patients allocated to a profound NMB received a moderate block and in two patients neuromuscular monitoring failed. The as-treated analysis revealed that pain scores were significantly lower at 6, 24 and 48 h after surgery. Moreover, the quality of recovery was significantly better at postoperative day 2 in patients receiving a profound versus moderate block (179.5 ±â€Š13.6 versus 172.3 ±â€Š19.2). CONCLUSION: Secondary analysis indicates that an adequately maintained profound neuromuscular block improves postoperative pain scores and quality of recovery. As the intention-to-treat analysis did not reveal a difference regarding the primary endpoint, future studies should pursue whether a thoroughly maintained profound NMB during laparoscopy improves relevant patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02838134.

Certification Training and Liver Transplant Experience Improves Liver Procurement Outcomes: The Dutch Approach.

BACKGROUND: This study investigates the impact of certification training and liver transplant experience on procurement outcomes of deceased donor liver procurement in the Netherlands. METHODS: Three groups (trainee, certified, and master) were formed, with further subdivision based on liver transplant experience. Three key outcomes-surgical injury, graft discard after injury, and donor hepatectomy duration-were analyzed. RESULTS: There were no significant differences in surgical graft injury in the three groups (trainee, 16.9%; certified, 14.8%; master, 18.2%; P = 0.357; 2011 to 2018). The only predictor for surgical graft injury was donation after cardiac death (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.10-2.02). Of the three groups, the master group had the highest discard rate after surgical injury (trainee, 0%; certified, 1.3%; master, 2.8%; P = 0.013). Master group without liver transplant experience (OR, 3.16; 95% CI, 1.21-8.27) and male donor sex (OR, 3.58; 95% CI, 1.32-9.73) were independent risk factors for discarding livers after surgical injury. Independent predictors for shorter hepatectomy durations included donors older than 50 years (coefficient [Coeff], -7.04; 95% CI, -8.03 to -3.29; P < 0.001), and master group (Coeff, -9.84; 95% CI, -14.37 to -5.31; P < 0.001) and certified group with liver transplant experience (Coeff, -6.54; 95% CI, -10.83 to -2.26; P = 0.003). On the other hand, master group without liver transplant experience (Coeff, 5.00; 95% CI, 1.03-8.96; P = 0.014) and donation after cardiac death (Coeff, 10.81; 95% CI, 8.32-13.3; P < 0.001) were associated with longer hepatectomy durations. CONCLUSIONS: Training and certification in abdominal organ procurement surgery were associated with a reduced discard rate for surgical injured livers and shorter hepatectomy times. The contrast between master group with and without liver transplant experience underscores the need for specialized training in this field.

A randomized clinical trial of living donor nephrectomy: a plea for a differentiated appraisal of mini-open muscle splitting incision and hand-assisted laparoscopic donor nephrectomy.

A randomized controlled trial was designed to compare various outcome variables of the retroperitoneal mini-open muscle splitting incision (MSI) technique and the transperitoneal hand-assisted laparoscopic technique (HAL) in performing living donor nephrectomies. Fifty living kidney donors were randomized to MSI or HAL. Primary endpoint was pain experience scored on a visual analogue scale (VAS). After MSI living donors indicated lower median (range) VAS scores at rest than HAL living donors on postoperative day 2.5 [10 (0-44) vs. 15 (0-70), P = 0.043] and day 3 [7 (0-28) vs. 10 (0-91), P = 0.023] and lower VAS scores while coughing on postoperative day 3 [20 (0-73) vs. 42 (6-86), P = 0.001], day 7 [8 (0-66) vs. 33 (3-76), P < 0.001] and day 14 [2 (0-17) vs. 12 (0-51), P = 0.009]. The MSI technique also resulted in reduced morphine requirement, better scores on three domains of the RAND-36, reduced costs and reduced CRP and IL-6 levels. The HAL technique was superior in operating time and postoperative decrease of hemoglobin level. The MSI technique is superior to the HAL technique in performing living donor nephrectomies with regard to postoperative pain experience. This study reopens the discussion of the way to go in performing the living donor nephrectomy.

Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation.

BACKGROUND: Kidneys derived from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Strikingly, early and profound serum levels of IL-6 in brain-dead donors are observed. IL-6 is the main regulator of the acute phase response (APR). The aim of this translational study was to investigate the expression of renal acute phase proteins (APPs) following brain death (BD) and to assess the association with renal allograft outcome after transplantation. METHODS: BD was induced in rats by inflating a subdurally placed balloon catheter. Kidney biopsies were obtained from human living and brain-dead donors at donation, after cold preservation and reperfusion. In vitro, renal proximal tubular epithelial cells (HK-2 cells) were stimulated with IL-6. RESULTS: Both in human and rat brain-dead donors, C3 and FBG expression was enhanced at donation compared to living donors and sham-operated animals. In human donors, no additional expression was found after cold ischaemia or reperfusion. C3 expression after reperfusion was independently associated with decreased short-term function after transplantation in grafts from brain-dead donors. In cultured HK-2 cells, C3 production was induced in the presence of IL-6. CONCLUSIONS: In conclusion, BD induces renal C3 and FBG expression. Moreover, C3 expression is associated with a worse allograft function early after transplantation. Therefore, targeting renal APPs in brain-dead donors, especially complement C3, may improve transplant outcome.

Heparin binding epidermal growth factor in renal ischaemia/reperfusion injury.

The epidermal growth factor (EGF) receptor and its ligands are crucially involved in the renal response to ischaemia. We studied the heparin binding-epidermal growth factor (HB-EGF), a major ligand for the EGF receptor, in experimental and human ischaemia/reperfusion injury (IRI). HB-EGF mRNA and protein expression was studied in rat kidneys and cultured human tubular (HK-2) cells that were subjected to IRI and in human donor kidneys during transplantation. The effect of EGF receptor inhibition was investigated in vivo and in vitro. Furthermore, urinary HB-EGF protein excretion was studied after renal transplantation. Finally, HB-EGF KO and WT mice were subjected to IRI to study the role of HB-EGF in renal injury. HB-EGF mRNA was significantly up-regulated in the early phase of IRI in rats, cells, and human donor biopsies. Treatment with PKI-166 reduces macrophage accumulation and interstitial alpha-SMA in the early phase of IRI in rats. In vitro, PKI-166 causes a marked reduction in HB-EGF-induced cellular proliferation. Urinary HB-EGF is increased after transplantation compared with control urines from healthy subjects. HB-EGF KO mice subjected to IRI revealed significantly less morphological damage after IRI, compared with WT mice. We conclude that IRI results in early induction of HB-EGF mRNA and protein in vivo and in vitro. Absence of HB-EGF and inhibition of the EGF receptor in the early phase of IRI has protective effects, suggesting a modulating role for HB-EGF.

How important is the duration of the brain death period for the outcome in kidney transplantation?

In kidney transplantation, graft survival using grafts from donation after brain death (DBD) donors is inferior to results after living donation. However, little is known about the effect of the duration of brain death (BDdur) on outcome after transplantation. This is a retrospective Organ Procurement and Transplant Network analysis using kidney donor and recipient data from 1994 to 2006. BDdur was calculated as the period between brain death declaration and aortic cross clamp. Effects of BDdur on delayed graft function (DGF), acute rejection and graft failure were calculated using binary logistic regression and Cox regression models. Median BDdur was 23.8 h. Longer BDdur decreased the risk for DGF and 1- and 3-year graft failure slightly, but not for acute rejection. In multivariate analysis, donor age and acute rejection were confounders. However, in a multivariate subgroup analysis of donors aged ≤ 55 years BDdur independently predicted DGF; each hour of BDdur decreasing the risk of DGF with 0.4% (P = 0.008). Longer BDdur is not detrimental and in fact slightly beneficial in DBD donors ≤ 55 years of age, reducing the chance of DGF in the recipient. This finding may have an impact on organ retrieval procedures, as no rush but rather an improved donor management prior to retrieval will benefit donor kidney viability.

Donor pretreatment with carbamylated erythropoietin in a brain death model reduces inflammation more effectively than erythropoietin while preserving renal function.

OBJECTIVE: We hypothesized that donor treatment of deceased brain dead donors would lead to a decrease in inflammatory responses seen in brain death and lead to a restoration of kidney function. DESIGN: A standardized slow-induction rat brain death model followed by evaluation of kidney function in an isolated perfused kidney model. SETTINGS: Surgery Research Laboratory, University Medical Center Groningen, the Netherlands. SUBJECTS: Male Fisher rats. INTERVENTIONS: Donor treatment with erythropoietin, carbamylated erythropoietin, which lacks erythropoietic activity, or vehicle. MEASUREMENTS AND MAIN RESULTS: In brain death, carbamylated erythropoietin and, to a lesser extent, erythropoietin were able to decrease the expression of several proinflammatory genes and to decrease the infiltration of polymorphonuclear cells in the kidney. No effect on tubular injury parameters was seen. Kidney function decreased almost by 50% after brain death but was fully restored after treatment with both carbamylated erythropoietin and erythropoietin. CONCLUSIONS: Carbamylated erythropoietin can inhibit the inflammatory response caused by brain death more effectively than erythropoietin, whereas both substances can restore kidney function after brain death.

Effect of brain death on gene expression and tissue activation in human donor kidneys.

BACKGROUND: After kidney transplantation, decreased graft survival is seen in grafts from brain dead (BD) donors compared with living donors. This might result partly from a progressive nonspecific inflammation in the graft. In this study, we focused on the effects of BD on inflammatory response (adhesion molecules, leukocyte invasion, gene expression) and stress-related heat shock proteins in the human kidney. Research outcomes and clinical donor parameters were then linked to outcome data after transplantation. METHODS: Kidney biopsy specimens and serum were obtained during organ retrieval from BD and living organ donor controls. Immunohistochemistry and semiquantitative reverse transcriptase-polymerase chain reaction were performed on the biopsy specimens. Clinical and laboratory parameters from BD donors were recorded and connected to outcome data of the recipients of the kidneys studied. RESULTS: After brain death, immunohistochemistry showed an increase of E-selectin (P<0.01) and interstitial leukocyte invasion (P<0.05) compared with controls. Also, reverse transcriptase-polymerase chain reaction showed a threefold increased heme oxygenase-1 (P<0.05) and Hsp70 (P<0.01) gene expression after BD. Levels of monocyte chemotactic protein-1 and transforming growth factor-beta were twice as high after brain death but did not reach significance. Transplantation outcome was influenced by several donor variables: positively most notably by donor treatment with desmopressin and negatively by high serum urea levels during brain death and by high intercellular adhesion molecule and vascular cell adhesion molecule expression in the kidney. Heme oxygenase-1 proved to have a protective function, but only in kidneys from living donors. CONCLUSIONS: The presence of interstitial leukocytes and the early adhesion molecule E-selectin in BD donor kidneys indicates an early-phase inflammatory process during organ retrieval. Elevated levels of monocyte chemotactic protein-1 and transforming growth factor-beta suggest a role for monocytes/macrophages in this phase. We suggest that BD causes a stress-related response against which protective heat shock proteins are formed in the future graft. This stress response may be too severe to be fully counteracted by elevated heat shock proteins. Which systemic and/or local factors trigger brain death-related graft injury is currently under investigation.