Hyperspectral Imaging (HSI) of Human Kidney Allografts.

OBJECTIVE: Aim of our study was to test a noninvasive HSI technique as an intraoperative real time assessment tool for deceased donor kidney quality and function in human kidney allotransplantation. SUMMARY OF BACKGROUND DATA: HSI is capable to deliver quantitative diagnostic information about tissue pathology, morphology, and composition, based on the spectral characteristics of the investigated tissue. Because tools for objective intraoperative graft viability and performance assessment are lacking, we applied this novel technique to human kidney transplantation. METHODS: Hyperspectral images of distinct components of kidney allografts (parenchyma, ureter) were acquired 15 and 45 minutes after reperfusion and subsequently analyzed using specialized HSI acquisition software capable to compute oxygen saturation levels (StO2), near infrared perfusion indices (NIR), organ hemoglobin indices, and tissue water indices of explored tissues. RESULTS: Seventeen kidney transplants were analyzed. Median recipient and donor age were 55 years. Cold ischemia time was 10.8 ±â€Š4.1 hours and anastomosis time was 35 ±â€Š7 minutes (mean ±â€Šstandard deviation). Two patients (11.8%) developed delayed graft function (DGF). cold ischemia time was significantly longer (18.6 ±â€Š1.6) in patients with DGF (P < 0.01). Kidneys with DGF furthermore displayed significant lower StO2 (P = 0.02) and NIR perfusion indices, 15 minutes after reperfusion (P < 0.01). Transplant ureters displayed a significant decrease of NIR perfusion with increased distance to the renal pelvis, identifying well and poor perfused segments. CONCLUSION: Intraoperative HSI is feasible and meaningful to predict DGF in renal allografts. Furthermore, it can be utilized for image guided surgery, providing information about tissue oxygenation, perfusion, hemoglobin concentration, and water concentration, hence allowing intraoperative viability assessment of the kidney parenchyma and the ureter.

Pre-operative ankle-brachial index for cardiovascular risk assessment in simultaneous pancreas-kidney transplant recipients: a simple and elegant strategy!

BACKGROUND: Patients with insulin-dependent diabetes mellitus type 1 (IDDM1) and end-stage kidney disease (ESKD) undergoing simultaneous pancreas kidney transplantation (SPKT) are a population with diffuse atherosclerosis and elevated risk of cardio- and cerebrovascular morbidity and mortality. We aimed to investigate the feasibility of preoperative screening for peripheral arterial disease (PAD), specifically ankle-brachial index (ABI) testing, to predict peri- and postoperative outcomes in SPKT recipients. METHODS: Medical data (2000-2016) from all patients with IDDM and ESKD undergoing SPKT at our transplant center were retrospectively analyzed. The correlation between PAD (defined by an abnormal ABI before SPKT and graft failure and mortality rates as primary end points, and the occurrence of acute myocardial infarction, cerebrovascular and peripheral vascular complications as secondary end points were investigated after adjustment for known cardiovascular risk factors. RESULTS: Among 101 SPKT recipients in our transplant population who underwent structured physiological arterial studies, 17 patients (17%) were diagnosed with PAD before transplantation. PAD, as defined by a low ABI index, was an independent and significant predictor of death (HR, 2.99 (95% CI 1.00-8.87), p = 0.049) and pancreas graft failure (HR, 4.3 (95% CI 1.24-14.91), p = 0.022). No significant differences were observed for kidney graft failure (HR 1.85 (95% CI 0.76-4.50), p = 0.178). In terms of the secondary outcomes, patients with PAD were more likely to have myocardial infarction, stroke, limb ischemia, gangrene or amputation (HR, 2.90 (95% CI 1.19-7.04), p = 0.019). CONCLUSIONS: Pre-transplant screening for PAD and cardiovascular risk factors with non-invasive ABI testing may help to reduce perioperative complications in high-risk patients. Future research on long-term outcomes might provide more in depth insights in optimal treatment strategies for PAD among SPKT recipients.

Impact of pre-transplant dialysis modality on the outcome and health-related quality of life of patients after simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) profoundly improves the health-related quality of life (HRQoL) of recipients. However, the influence of the pre-transplant dialysis modality on the success of the SPKT and post-transplant HRQoL remains unknown. METHODS: We analyzed the surgical outcome, long-term survival, as well as HRQoL of 83 SPKTs that were performed in our hospital between 2000 and 2016. Prior to transplant, 64 patients received hemodialysis (HD) and nineteen patients received peritoneal dialysis (PD). Physical and mental quality of life results from eight basic scales and the physical and mental component summaries (PCS and MCS) were measured using the Short Form 36 (SF-36) survey. RESULTS: Peri- and postoperative complications, as well as patient and graft survival were similar between the two groups. Both groups showed an improvement of HRQoL in all SF-36 domains after transplantation. Compared with patients who received HD before transplantation, PD patients showed significantly better results in four of the eight SF-36 domains: physical functioning (mean difference HD - PD: - 12.4 ± 4.9, P = < 0.01), bodily pain (- 14.2 ± 6.3, P < 0.01), general health (- 6.3 ± 2.8, P = 0.04), vitality (- 6.8 ± 2.6, P = 0.04), and PCS (- 5.2 ± 1.5, P < 0.01) after SPKT. In the overall study population, graft loss was associated with significant worsening of the HRQoL in all physical components (each P < 0.01). CONCLUSIONS: The results of this analysis show that pre-transplant dialysis modality has no influence on the outcome and survival rate after SPKT. Regarding HRQoL, patients receiving PD prior to SPKT seem to have a slight advantage compared with patients with HD before transplantation.

Short and long-term metabolic outcomes in patients with type 1 and type 2 diabetes receiving a simultaneous pancreas kidney allograft.

BACKGROUND: In contrast to insulin-dependent type 1 diabetes mellitus (T1DM), the indication for Simultaneous pancreas-kidney transplantation (SPK) in patients with type 2 diabetes mellitus (T2DM) is still ambiguous and wisely Eurotransplant (ET) only granted transplant-permission in a selected group of patients. However, with regard to improvement of metabolic conditions SPK might still be a considerable treatment option for lean insulin dependent type 2 diabetics suffering from renal disease. METHODS: Medical data (2001-2013) from all consecutive T1DM and T2DM patients who received a SPK or kidney transplant alone (KTA) at the University Hospital of Leipzig were analyzed. Donor, recipients and long-term endocrine, metabolic and graft outcomes were investigated for T1DM and T2DM-SPK recipients (transplanted upon a special request allocation by ET) and T2DM patients who received a KTA during the same period. RESULTS: Eighty nine T1DM and 12 T2DM patients received a SPK and 26 T2DM patients received a KTA. Patient survival at 1 and 5 years was 89.9 and 88.8% for the T1DM group, 91.7 and 83.3% for the T2DM group, and 92.3 and 69.2% for the T2DM KTA group, respectively (p < 0.01). Actuarial pancreas graft survival for SPK recipients at 1 and 5 years was 83.1 and 78.7% for the T1DM group and 91.7 and 83.3% for the T2DM group, respectively (p = 0.71). Kidney allograft survival at 5 years was 79.8% for T1DM, 83.3% for T2DM, and 65.4% for T2DM KTA (p < 0.01). Delayed graft function (DGF) rate was significantly higher in type 2 diabetics received a KTA. Surgical, immunological and infectious complications showed similar results for T1DM and T2DM recipients after SPK transplant and KTA, respectively. With regard to the lipid profile, the mean high-density lipoprotein (HDL)- cholesterol levels were significantly higher in T1DM recipients compared to T2DM patients before transplantation (p = 0.02) and remained significantly during follow up period. CONCLUSION: Our data demonstrate that with regard to metabolic function a selected group of patients with T2DM benefit from SPK transplantation. Consensus guidelines and further studies for SPK transplant indications in T2DM patients are still warranted.

Effects of simultaneous pancreas-kidney transplantation and kidney transplantation alone on the outcome of peripheral vascular diseases.

BACKGROUND: The effects of Simultaneous Pancreas Kidney Transplantation (SPKT) on Peripheral Vascular Disease (PVD) warrants additional study and more target focus, since little is known about the mid- and long-term effects on the progression of PVD after transplantation. METHODS: 101 SPKT and 26 Kidney Transplantation Alone (KTA) recipients with insulin-dependent diabetes mellitus (IDDM) were retrospectively evaluated with regard to graft and metabolic outcome. Special subgroup analysis was directed towards the development and progression of peripheral vascular complications (PVC) (amputation, ischemic ulceration, lower extremity angioplasty/ bypass surgery) after transplantation. RESULTS: The 10-year patient survival was significantly higher in the SPKT group (SPKT: 82% versus KTA 40%; P < 0.001). KTA recipients had a higher prevalence of atherosclerotic risk factors, including coronary artery disease (P < 0.001), higher serum triglyceride levels (P = 0.049), higher systolic (P = 0.03) and diastolic (P = 0.02) blood pressure levels. The incidence of PVD before transplantation was comparable between both groups (P = 0.114). Risk factor adjusted multivariate analysis revealed that patients with SPKT had a significant lower amount (32%) of PVCs (32 PVCs in 21 out of 101 SPKT; P < 0.001) when compared to the KTA patients who developed a significant increase in PVCs to 69% of cases (18 PVCs in 11 out of 26 KTA; P < 0.001). In line mean values of HbA1c (P < 0.01) and serum triglycerides (P < 0.01) were significantly lower in patients with SPKT > 8 years after transplantation. CONCLUSION: SPKT favorably slows down development and progression of PVD by maintaining a superior metabolic vascular risk profile in patients with IDDM1.

Hyperspectral Evaluation of the Human Liver During Major Resection.

Objective: This study investigates the effects of PVE and vascular inflow control (VIC) on liver microperfusion and tissue oxygenation using hyperspectral imaging (HSI) technology. Background: Mechanisms triggering future liver remnant (FLR) augmentation introduced by PVE have not been sufficiently studied in humans. Particularly, the arterial buffer response (ABR) of the liver might play a vital role. Methods: Hyperspectral datacubes (TIVITA) acquired during 58 major liver resections were qualitatively and quantitatively analyzed for tissue oxygenation (StO2%), near-infrared (NIR) perfusion, organ-hemoglobin indices (OHI), and tissue-water indices (TWI). The primary study endpoint was measurement of hyperspectral differences in liver parenchyma subject to PVE and VIC before resection. Results: HSI revealed parenchyma specific differences in StO2% with regard to the underlying disease (P < 0.001). Preoperative PVE (n = 23, 40%) lead to arterial hyperoxygenation and hyperperfusion of corresponding liver segments (StO2: 77.23% ± 11.93%, NIR: 0.46 ± 0.20[I]) when compared with the FLR (StO2: 66.13% ± 9.96%, NIR: 0.23 ± 0.12[I]; P < 0.001). In a case of insufficient PVE and the absence of FLR augmentation hyperspectral StO2 and NIR differences were absent. The hyperspectral assessment demonstrated increased liver tissue-oxygenation and perfusion in PVE-segments (n = 23 cases) and decreased total VIC in nonembolized FLR hemilivers (n = 35 cases; P < 0.001). Intraoperative HSI analysis of tumor tissue revealed marked tumor specific differences in StO2, NIR, OHI, and TWI (P < 0.001). Conclusions: HSI allows intraoperative quantitative and qualitative assessment of microperfusion and StO2% of liver tissue. PVE lead to ABR-triggered tissue hyperoxygenation and cross-talk FLR augmentation. HSI furthermore facilitates intraoperative tumor tissue identification and enables image-guided liver surgery following VIC.

Influence of Intraoperative Hemodynamic Parameters on Outcome in Simultaneous Pancreas-Kidney Transplant Recipients.

Objectives: Adequate organ perfusion, as well as appropriate blood pressure levels at the time of unclamping, is crucial for early and long-term graft function and outcome in simultaneous pancreas−kidney transplantation (SPKT). However, the optimal intraoperative mean arterial pressure (MAP) level has not well been defined. Methods: From a prospectively collected database, the medical data of 105 patients undergoing SPKT at our center were retrospectively analyzed. A receiver operating characteristic (ROC) analysis was preliminarily performed for optimal cut-off value for MAP at reperfusion, to predict early pancreatic graft function. Due to these results, we divided the patients according to their MAP values at reperfusion into <91 mmHg (n = 47 patients) and >91 mmHg (n = 58 patients) groups. Clinicopathological characteristics and outcomes, as well as early graft function and long-term survival, were retrospectively analyzed. Results: Donor and recipient characteristics were comparable between both groups. Rates of postoperative complications were significantly higher in the <91 mmHg group than those in the >91 mmHg group (vascular thrombosis of the pancreas: 7 (14%) versus 2 (3%); p = 0.03; pancreatitis/intraabdominal abscess: 10 (21%) versus 4 (7%); p = 0.03; renal delayed graft function (DGF): 11 (23%) versus 5 (9%); p = 0.03; postreperfusion urine output: 106 ± 50 mL versus 195 ± 45 mL; p = 0.04). There were no significant differences in intraoperative volume repletion, central venous pressure (CVP), use of vasoactive inotropic agents, and the metabolic outcome. Five-year pancreas graft survival was significantly higher in the >91 mmHg group (>91 mmHg: 82% versus <91 mmHg: 61%; p < 0.01). No significant differences were observed in patient and kidney graft survival at 5 years between both groups. Multivariate Cox regression analysis affirmed MAP < 91 mmHg as an independent prognostic predictor for renal DGF (HR 3.49, 1.1−10.8, p = 0.03) and pancreas allograft failure (HR 2.26, 1.0−4.8, p = 0.01). Conclusions: A MAP > 91 mmHg at the time point of reperfusion was associated with a reduced rate of postoperative complications, enhancing and recovering long-term graft function and outcome and thus increasing long-term survival in SPKT recipients.

Intraoperative reperfusion assessment of human pancreas allografts using hyperspectral imaging (HSI).

Background: The most common causes of early graft loss in pancreas transplantation are insufficient blood supply and leakage of the intestinal anastomosis. Therefore, it is critical to monitor graft perfusion and oxygenation during the early post-transplant period. The goal of our pilot study was to evaluate the utility of hyperspectral imaging (HSI) in monitoring the microcirculation of the graft and adequate perfusion of the intestinal anastomosis during pancreatic allotransplantation. Methods: We imaged pancreatic grafts and intestinal anastomosis in real-time in three consecutive, simultaneous pancreas-kidney transplantations using the TIVITA® HSI system. Further, the intraoperative oxygen saturation (StO2), tissue perfusion (near-infrared perfusion index, NIR), organ hemoglobin index (OHI), and tissue water index (TWI) were measured 15 minutes after reperfusion by HSI. Results: All pancreas grafts showed a high and homogeneous StO2 (92.6%±10.45%). Intraoperative HSI analysis of the intestinal anastomosis displayed significant differences of StO2 (graft duodenum 67.46%±5.60% vs. recipient jejunum: 75.93%±4.71%, P<0.001) and TWI {graft duodenum: 0.63±0.09 [I (Index)] vs. recipient jejunum: 0.72±0.09 [I], P<0.001}. NIR and OHI did not display remarkable differences {NIR duodenum: 0.68±0.06 [I] vs. NIR jejunum: 0.69±0.04 [I], P=0.747; OHI duodenum: 0.70±0.12 [I] vs. OHI jejunum: 0.68±0.13 [I], P=0.449}. All 3 patients had an uneventful postoperative course with one displaying a Banff 1a rejection which was responsive to steroid treatment. Conclusions: Our study shows that contact-free HSI has potential utility as a novel tool for real-time monitoring of human pancreatic grafts after reperfusion, which could improve the outcome of pancreas transplantation. Further investigations are required to determine the predictive value of intraoperative HSI imaging.

Correlation of Different Serum Biomarkers with Prediction of Early Pancreatic Graft Dysfunction Following Simultaneous Pancreas and Kidney Transplantation.

Background: Despite recent advances and refinements in perioperative management of simultaneous pancreas−kidney transplantation (SPKT) early pancreatic graft dysfunction (ePGD) remains a critical problem with serious impairment of early and long-term graft function and outcome. Hence, we evaluated a panel of classical blood serum markers for their value in predicting early graft dysfunction in patients undergoing SPKT. Methods: From a prospectively collected database medical data of 105 patients undergoing SPKT between 1998 and 2018 at our center were retrospectively analyzed. The primary study outcome was the detection of occurrence of early pancreatic graft dysfunction (ePGD), the secondary study outcome was early renal graft dysfunction (eRGD) as well as all other outcome parameters associated with the graft function. In this context, ePGD was defined as pancreas graft-related complications including graft pancreatitis, pancreatic abscess/peritonitis, delayed graft function, graft thrombosis, bleeding, rejection and the consecutive need for re-laparotomy due to graft-related complications within 3 months. With regard to analyzing ePGD, serum levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), pancreatic lipase as well as neutrophil−lymphocyte ratio (NLR) and platelet−lymphocyte ratio (PLR) were measured preoperatively and at postoperative days (POD) 1, 2, 3 and 5. Further, peak serum levels of CRP and lipase during the first 72 h were evaluated. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for ePGD and eRGD. Cut-off levels were calculated with the Youden index. Significant diagnostic biochemical cut-offs as well as other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 105 patients included, 43 patients (41%) and 28 patients (27%) developed ePGD and eRGD following SPKT, respectively. The mean WBC, PCT, NLR, PLR, CRP and lipase levels were significantly higher on most PODs in the ePGD group compared to the non-ePGD group. ROC analysis indicated that peak lipase (AUC: 0.82) and peak CRP levels (AUC: 0.89) were highly predictive for ePGD after SPKT. The combination of both achieved the highest AUC (0.92; p < 0.01) in predicting ePGD. Concerning eRGD, predictive accuracy of all analyzed serological markers was moderate (all AUC < 0.8). Additionally, multivariable analysis identified previous dialysis/no preemptive transplantation (OR 2.4 (95% CI: 1.41−4.01), p = 0.021), donor age (OR 1.07 (95% CI: 1.03−1.14), p < 0.010), donor body mass index (OR 1.32 (95% CI: 1.01−1.072), p = 0.04), donors cerebrovascular cause of death (OR 7.8 (95% CI: 2.21−26.9), p < 0.010), donor length of ICU stay (OR 1.27 (95% CI: 1.08−1.49), p < 0.010), as well as CIT pancreas (OR 1.07 (95% CI: 1.03−1.14), p < 0.010) as clinical relevant prognostic predictors for ePGD. Further, a peak of lipase (OR 1.04 (95% CI: 1.02−1.07), p < 0.010), peak of CRP levels (OR 1.12 (95% CI: 1.02−1.23), p < 0.010), pancreatic serum lipase concentration on POD 2 > 150 IU/L (OR 2.9 (95% CI: 1.2−7.13), p = 0.021) and CRP levels of ≥ 180 ng/mL on POD 2 (OR 3.6 (95% CI: 1.54−8.34), p < 0.01) and CRP levels > 150 ng/mL on POD 3 (OR 4.5 (95% CI: 1.7−11.4), p < 0.01) were revealed as independent biochemical predictive variables for ePGD after transplantation. Conclusions: In the current study, the combination of peak lipase and CRP levels were highly effective in predicting early pancreatic graft dysfunction development following SPKT. In contrast, for early renal graft dysfunction the predictive value of this parameter was less sensitive. Intensified monitoring of these parameters may be helpful for identifying patients at a higher risk of pancreatic ischemia reperfusion injury and various IRI- associated postoperative complications leading to ePGD and thus deteriorated outcome.

Analysis of Volatile Anesthetic-Induced Organ Protection in Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia-reperfusion injury (IRI)-Remains a common cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients. METHODS: Medical data of 105 patients undergoing SPKT between 1998-2018 were retrospectively analyzed and stratified according to the used VAs. The primary study endpoint was the association and effect of VAs on pancreas allograft failure following SPKT; secondary endpoint analyses included "IRI- associated posttransplant clinical outcome" as well as long-term graft function and outcome. Additionally, peak serum levels of C-reactive protein (CRP) and lipase during the first 72 h after SPKT were determined and used as further markers for "pancreatic IRI" and graft injury. Typical clinicopathological characteristics and postoperative outcomes such as early graft outcome and long-term function were analyzed. RESULTS: Of the 105 included patients in this study three VAs were used: isoflurane (n = 58 patients; 55%), sevoflurane (n = 22 patients; 21%), and desflurane (n = 25 patients, 24%). Donor and recipient characteristics were comparable between both groups. Early graft loss within 3 months (24% versus 5% versus 8%, p = 0.04) as well as IRI-associated postoperative clinical complications (pancreatitis: 21% versus 5% versus 5%, p = 0.04; vascular thrombosis: 13% versus 0% versus 5%; p = 0.09) occurred more frequently in the Isoflurane group compared with the sevoflurane and desflurane groups. Anesthesia with sevoflurane resulted in the lowest serum peak levels of lipase and CRP during the first 3 days after transplantation, followed by desflurane and isoflurane (p = 0.039 and p = 0.001, respectively). There was no difference with regard to 10-year pancreas graft survival as well as endocrine/metabolic function among all three VA groups. Multivariate analysis revealed the choice of VAs as an independent prognostic factor for graft failure three months after SPKT (HR 0.38, 95%CI: 0.17-0.84; p = 0.029). CONCLUSIONS: In our study, sevoflurane and desflurane were associated with significantly increased early graft survival as well as decreased IRI-associated post-transplant clinical outcomes when compared with the isoflurane group and should be the focus of future clinical studies evaluating the positive effects of different VA agents in patients receiving SPKT.

Impact of Body Mass Index on Tumor Recurrence in Patients Undergoing Liver Resection for Perihilar Cholangiocarcinoma (pCCA).

BACKGROUND: The association of body mass index (BMI) and long-term prognosis and outcome of patients with perihilar cholangiocarcinoma (pCCA) has not been well defined. The aim of this study was to evaluate clinicopathologic and oncologic outcomes with pCCA undergoing resection, according to their BMI. METHODS: Patients undergoing liver resection in curative intention for pCCA at a tertiary German hepatobiliary (HPB) center were identified from a prospective database. Patients were classified as normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (>30 kg/m2) according to their BMI. Impact of clinical and histo-pathological characteristics on recurrence-free survival (RFS) were assessed using Cox proportional hazard regression analysis among patients of all BMI groups. RESULTS: Among a total of 95 patients undergoing liver resection in curative intention for pCCA in the analytic cohort, 48 patients (50.5%) had normal weight, 33 (34.7%) were overweight and 14 patients (14.7%) were obese. After a median follow-up of 4.3 ± 2.9 years, recurrence was observed in totally 53 patients (56%). The cumulative recurrence probability was higher in obese and overweight patients than normal weight patients (5-year recurrence rate: obese: 82% versus overweight: 81% versus normal weight: 58% at 5 years; p = 0.02). Totally, 1-, 3-, 5- and 10-year recurrence-free survival rates were 68.5%, 44.6%, 28.9% and 13%, respectively. On multivariable analysis, increased BMI (HR 1.08, 95% CI: 1.01-1.16; p = 0.021), poor/moderate tumor differentiation (HR 2.49, 95% CI: 1.2-5.2; p = 0.014), positive lymph node status (HR 2.01, 95% CI: 1.11-3.65; p = 0.021), positive resection margins (HR 1.89, 95% CI:1.02-3.4; p = 0.019) and positive perineural invasion (HR 2.92, 95% CI: 1.02-8.3; p = 0.045) were independent prognostic risk factors for inferior RFS. CONCLUSION: Our study shows that a high BMI is significantly associated with an increased risk of recurrence after liver resection in curative intention for pCCA. This factor should be considered in future studies to better predict patient's individual prognosis and outcome based on their BMI.

The Value of Graft Implantation Sequence in Simultaneous Pancreas-Kidney Transplantation on the Outcome and Graft Survival.

BACKGROUND/OBJECTIVES: The sequence of graft implantation in simultaneous pancreas-kidney transplantation (SPKT) warrants additional study and more targeted focus, since little is known about the short- and long-term effects on the outcome and graft survival after transplantation. MATERIAL AND METHODS: 103 patients receiving SPKT in our department between 1999 and 2015 were included in the study. Patients were divided according to the sequence of graft implantation into pancreas-first (PF, n = 61) and kidney-first (KF, n = 42) groups. Clinicopathological characteristics, outcome and survival were reviewed retrospectively. RESULTS: Donor and recipient characteristics were similar. Rates of post-operative complications and graft dysfunction were significantly higher in the PF group compared with the KF group (episodes of acute rejection within the first year after SPKT: 11 (18%) versus 2 (4.8%); graft pancreatitis: 18 (18%) versus 2 (4.8%), p = 0.04; vascular thrombosis of the pancreas: 9 (14.8%) versus 1 (2.4%), p = 0.03; and delayed graft function of the kidney: 12 (19.6%) versus 2 (4.8%), p = 0.019). The three-month pancreas graft survival was significantly higher in the KF group (PF: 77% versus KF: 92.1%; p = 0.037). No significant difference was observed in pancreas graft survival five years after transplantation (PF: 71.6% versus KF: 84.8%; p = 0.104). Kidney graft survival was similar between the two groups. Multivariate analysis revealed order of graft implantation as an independent prognostic factor for graft survival three months after SPKT (HR 2.6, 1.3-17.1, p = 0.026) and five years (HR 3.7, 2.1-23.4, p = 0.040). CONCLUSION: Our data indicates that implantation of the pancreas prior to the kidney during SPKT has an influence especially on the early-post-operative outcome and survival rate of pancreas grafts.

Robotic assisted nephrectomy for living kidney donation (RANLD) with use of multiple locking clips or ligatures for renal vascular closure.

BACKGROUND: Robotic assisted nephrectomy for living donation (RANLD) is a rapid emerging surgical technique competing for supremacy with totally laparoscopic and laparoscopic hand assisted techniques. Opinions about the safety of specific techniques of vascular closure in minimally invasive living kidney donation are heterogeneous and may be different for laparoscopic and robotic assisted surgical techniques. METHODS: We retrospectively analyzed perioperative and short-term outcomes of our first (n=40) RANLD performed with the da Vinci Si surgical platform. Vascular closure of renal vessels was performed by either double clipping or a combination of clips and non-transfixing suture ligatures. RESULTS: RANLD almost quintupled in our center for the observed time period. A total of n=21 (52.5%) left and n=19 (47.5%) right kidneys were procured. Renal vessel sealing with two locking clips was performed in 18 cases (45%) Both, clips and non-transfixing ligatures were used in 22 cases (55%). Mean donor age was 53.075±11.68 years (range, 28-70). The average total operative time was 150.75±27.30 min. Right donor nephrectomy (139±22 min) was performed significantly faster than left (160.95±27.93 min, P=0.01). Warm ischemia time was similar for both vascular sealing techniques and did not differ between left and right nephrectomies. No conversion was necessary. Clavien-Dindo Grade ≤IIIb complications occurred in (n=5) 12.5%. Grade IV and V complications did not develop. In particular no hemorrhage occurred using multiple locking clips or suture ligatures for renal vascular closure. Mortality was 0%. Thirteen kidneys (32.5%) were transplanted across the AB0 barrier. CONCLUSIONS: RANLD is an emerging minimally invasive surgical technique which facilitates excellent perioperative and short-term outcomes also when using multiple locking clips or suture ligatures for renal vascular closure.

Autoimmune Hepatitis-Immunologically Triggered Liver Pathogenesis-Diagnostic and Therapeutic Strategies.

Autoimmune hepatitis (AIH) is a severe liver disease that arises in genetically predisposed male and female individuals worldwide. Diagnosis of AIH is made clinically applying diagnostic scores; however, the heterotopic disease phenotype often makes a rapid determination of disease challenging. AIH responds favorably to steroids and pharmacologic immunosuppression, and liver transplantation is only necessary in cases with acute liver failure or end-stage liver cirrhosis. Recurrence or development of de novo AIH after transplantation is possible, and treatment is similar to standard AIH therapy. Current experimental investigations of T cell-mediated autoimmune pathways and analysis of changes within the intestinal microbiome might advance our knowledge on the pathogenesis of AIH and trigger a spark of hope for novel therapeutic strategies.