Microtubule-associated protein 1B dysregulates microtubule dynamics and neuronal mitochondrial transport in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a devastating childhood disease primarily affecting lower motoneurons in the spinal cord. SMA is caused by the loss of functional survival of motoneuron (SMN) protein, leading to structural and functional alterations of the cytoskeleton in motoneurons and other cells. Loss of SMN results in impairments of microtubule architecture, but the underlying mechanisms are not completely understood. In this study, we mechanistically analyzed the effects of SMN deficiency on microtubules, demonstrating a reduced stability together with a reduction in alpha tubulin detyrosination. This was caused by increased levels of microtubule-associated protein 1B and tubulin tyrosine ligase, resulting in mitochondrial mislocalization in SMA. Our findings suggest that altered tubulin post-translational modifications and microtubule-associated proteins are involved in the pathomechanisms of SMA, such as an impaired axonal transport of mitochondria.

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.

Recipient obesity as a risk factor in kidney transplantation.

BACKGROUND: The aim of the study was to investigate the effect of recipient obesity on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). PATIENTS AND METHODS: A total of 578 patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into normal weight (BMI 18.5-24.9 kg/m2; N = 304), overweight (BMI 25-29.9 kg/m2; N = 205) and obese (BMI ≥ 30 kg/m2; N = 69) groups. Their clinicopathological characteristics, outcomes, and survival rates were analyzed retrospectively. RESULTS: Obesity was associated with an increased rate of surgical complications such as wound infection (P < 0.001), fascial dehiscence (P = 0.023), and lymphoceles (P = 0.010). Furthermore, the hospital stay duration was significantly longer in the groups with obese patients compared to normal weight and overweight patients (normal weight: 22 days, overweight: 25 days, and obese: 33 days, respectively; P < 0.001). Multivariate analysis showed that recipient obesity (BMI ≥ 30) was an independent prognostic factor for delayed graft function (DGF) (OR 2.400; 95% CI, 1.365-4.219; P = 0.002) and postoperative surgical complications (OR 2.514; 95% CI, 1.230-5.136; P = 0.011). The mean death-censored graft survival was significantly lower in obese patients (normal weight: 16.3 ± 0.6 years, overweight: 16.3 ± 0.8 years, obese 10.8 ± 1.5 years, respectively; P = 0.001). However, when using the Cox proportional hazards model, the association between recipient obesity and death-censored renal graft failure disappeared, after adjustment for important covariates, whereas the principal independent predictors of graft loss were recipient diabetes mellitus and hypertension and kidneys from donors with expanded donor criteria. CONCLUSION: In conclusion, obesity increases the risk of DGF and post-operative surgical complications after primary KT. Appropriate risk-adapted information concerning this must be provided to such patients before KT. Furthermore, obesity-typical concomitant diseases seem to negatively influence graft survival and need to be considered after the transplantation of obese patients.

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.

Current State and Future Possibilities in Liver Transplantation.

Due to medical and surgical progress, liver transplantation (LT) is is nowadays a routine treatment for terminal liver failure and hepatic malignancies. However, in recent years there has been a change in the indications for LT. Especially in western industrialized countries, the use of LT for chronic hepatis B and hepatitis C cirrhosis is continuously decreasing since the introduction of effective antiviral drugs. Liver cirrhosis due to non-alcoholic steatohepatitis (NASH), alcoholic liver disease and hepatocellular carcinoma (HCC) in cirrhosis are now among the leading indications for LT. Due to tremendous progress in oncology, immunology, and technical aspects, multidisciplinary cancer treatment increasingly includes LT for non-HCC hepatobiliary malignancies. Excellent 5-year survival rates of 75 to 80% can now be achieved after LT. However, in patients with liver cirrhosis, the implementation of a 'sickest first' principle for liver allocation has led to an increasing number of critically ill patients undergoing liver transplantation. This results in an increased morbidity and mortality after liver transplantation. Moreover, donor characteristics have markedly shifted to less ideal grafts due to an increasing shortage of donor organs in many countries. In this context, normothermic machine perfusion with oxygenated blood components using pulsatile flow has been shown to reduce liver damage despite a prolonged preservation time and might be able to provide viability testing for otherwise discarded organs. With favorable donor and recipient conditions, excellent long-term results can be obtained with a 10-year survival rate of close to 70%. However, in patients with a high MELD score (>30), survival rates markedly decrease by 12-18%. Future research should focus on optimization of organ allocation, optimization of immunosuppression including tolerance induction, and on increasing the donor organ pool to further improve and the numbers of successful LT.

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.

[Laparoscopic Left Hemihepatectoy Applying Intraoperative Indocyanine Green Fluorescence Detection Counter Perfusion Method for Visualization]. / Laparoskopische Hemihepatektomie links mit intraoperativer Indocyaningrün-Perfusionsbildgebung.

Intraoperative indocyanine green (ICG) fluorescence detection by the "counter perfusion method" is a useful tool to identify hepatic segments and intersegmental planes during anatomic liver resection. We report of a 54-year old patient with recurrent cholangitis due to Caroli disease, who underwent a laparoscopic hemihepatectomy. To determine the resection line and resection plane, we injected ICG intravenously after clamping/ligating the left hepatic artery and left portal vein. Before and during resection the liver was observed under visible light and under near-infrared (NIR) light. This method allowed for precise anatomical resection of non-perfused liver segments 2, 3 and 4.

Metalloprotease-mediated cleavage of PlexinD1 and its sequestration to actin rods in the motoneuron disease spinal muscular atrophy (SMA).

Cytoskeletal rearrangement during axon growth is mediated by guidance receptors and their ligands which act either as repellent, attractant or both. Regulation of the actin cytoskeleton is disturbed in Spinal Muscular Atrophy (SMA), a devastating neurodegenerative disease affecting mainly motoneurons, but receptor-ligand interactions leading to the dysregulation causing SMA are poorly understood. In this study, we analysed the role of the guidance receptor PlexinD1 in SMA pathogenesis. We showed that PlexinD1 is cleaved by metalloproteases in SMA and that this cleavage switches its function from an attractant to repellent. Moreover, we found that the PlexinD1 cleavage product binds to actin rods, pathological aggregate-like structures which had so far been described for age-related neurodegenerative diseases. Our data suggest a novel disease mechanism for SMA involving formation of actin rods as a molecular sink for a cleaved PlexinD1 fragment leading to dysregulation of receptor signaling.

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.

The 28-year incidence of de novo malignancies after liver transplantation: A single-center analysis of risk factors and mortality in 1616 patients.

De novo malignancies (DNMs) are one of the leading causes of late mortality after liver transplantation (LT). We analyzed 1616 consecutive patients who underwent LT between 1988 and 2006 at our institution. All patients were prospectively observed over a study period of 28 years by our own outpatient clinic. Complete follow-up data were available for 96% of patients, 3% were incomplete, and only 1% were lost to follow-up. The median follow-up of the patients was 14.1 years. Variables with possible prognostic impact on the development of DNMs were analyzed, as was the incidence of malignancies compared with the nontransplant population by using standardized incidence ratios. In total, 266 (16.5%) patients developed 322 DNMs of the following subgroups: hematological malignancies (n = 49), skin cancer (n = 83), and nonskin solid organ tumors (SOT; n = 190). The probability of developing any DNM within 10 and 25 years was 12.9% and 23.0%, respectively. The respective probability of developing SOT was 7.8% and 16.2%. Mean age at time of diagnosis of SOT was 57.4 years (range, 18.3-81.1 years). In the multivariate analysis, an increased recipient age (hazard ratio [HR], 1.03; P < 0.001) and a history of smoking (HR, 1.92; P < 0.001) were significantly associated with development of SOT. Moreover, the development of SOT was significantly increased in cyclosporine A-treated compared with tacrolimus-treated patients (HR, 1.53; P = 0.03). The present analysis shows a disproportionate increase of de novo SOT with an increasing follow-up period. Increased age and a history of smoking are confirmed as major risk factors. Moreover, the importance of immunosuppression is highlighted. Liver Transplantation 23 1404-1414 2017 AASLD.

The DNA index as a prognostic tool in hilar cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: Due to the devastating prognosis of patients suffering from hilar cholangiocarcinoma (HCCA) valid prognostic factors are urgently needed to guide treatment decisions in a personalized concept. The aim of this study was to analyze the predictive value of the DNA index in a large single-center cohort of patients undergoing resection of HCCA. METHODS: A total of 154 patients who underwent resection of HCCA were included in this prospective study. The DNA index was assessed by image cytometry of fresh tumor samples and correlated, as well as standard histopathological parameters, with patient survival. RESULTS: The median DNA index was 1.61 ± 0.32. Univariate survival analysis identified eight parameters including DNA index, but not DNA ploidy as prognostic markers. In the Cox proportional hazard model DNA index (P = 0.021), tumor size (P = 0.029) and lymph nodes status (P = 0.039) could be shown to be independent predictors of patient survival. CONCLUSION: The DNA index represents an independent prognostic marker in HCCA which is superior to most standard histopathological factors. Since the DNA index can be assessed not only post- but also preoperatively, it might be a potential tool in the preoperative decision-making process.

Does Timepoint of Surgical Procedure Affect the Outcome in Simultaneous Pancreas-Kidney Transplantation? A Retrospective Single-Center Analysis over 20 Years.

Background: Sleep deprivation and disturbances in circadian rhythms may hinder surgical performance and decision-making capabilities. Solid organ transplantations, which are technically demanding and often begin at uncertain times, frequently during nighttime hours, are particularly susceptible to these effects. This study aimed to assess how transplant operations conducted during daytime versus nighttime influence both patient and graft outcomes and function. Methods: simultaneous pancreas-kidney transplants (SPKTs) conducted at the University Hospital of Leipzig from 1998 to 2018 were reviewed retrospectively. The transplants were categorized based on whether they began during daytime hours (8 a.m. to 6 p.m.) or nighttime hours (6 p.m. to 8 a.m.). We analyzed the demographics of both donors and recipients, as well as primary outcomes, which included surgical complications, patient survival, and graft longevity. Results: In this research involving 105 patients, 43 SPKTs, accounting for 41%, took place in the daytime, while 62 transplants (59%) occurred at night. The characteristics of both donors and recipients were similar across the two groups. Further, the rate of (surgical) pancreas graft-related complications and reoperations (daytime 39.5% versus nighttime 33.9%; p = 0.552) were also not statistically significant between both groups. In this study, the five-year survival rate for patients was comparable for both daytime and nighttime surgeries, with 85.2% for daytime and 86% for nighttime procedures (p = 0.816). Similarly, the survival rates for pancreas grafts were 75% for daytime and 77% for nighttime operations (p = 0.912), and for kidney grafts, 76% during the day compared to 80% at night (p = 0.740), indicating no significant statistical difference between the two time periods. In a multivariable model, recipient BMI > 30 kg/m2, donor age, donor BMI, and cold ischemia time > 15 h were independent predictors for increased risk of (surgical) pancreas graft-related complications, whereas the timepoint of SPKT (daytime versus nighttime) did not have an impact. Conclusions: The findings from our retrospective analysis at a big single German transplant center indicate that SPKT is a reliable procedure, regardless of the start time. Additionally, our data revealed that patients undergoing nighttime transplants have no greater risk of surgical complications or inferior results concerning long-term survival of the patient and graft. However, due to the small number of cases evaluated, further studies are required to confirm these results.

The GALAD score and the BALAD-2 score correlate with transarterial and systemic treatment response and survival in patients with hepatocellular carcinoma.

PURPOSE: The GALAD score and the BALAD-2 score are biomarker-based scoring systems used to detect hepatocellular carcinoma (HCC). Both incorporate levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Our objective was to examine the relationship between the GALAD score as well as the BALAD-2 score and treatment response to transarterial or systemic treatments in patients with HCC. METHODS: A total of 220 patients with HCC treated with either transarterial (n = 121) or systemic treatments (n = 99; mainly Sorafenib) were retrospectively analyzed. The GALAD score and the BALAD-2 score were calculated based on AFP-L3, AFP, and DCP levels measured in serum samples collected before treatment. The results were correlated with 3-month treatment efficacy based on radiologic mRECIST criteria. RESULTS: The GALAD score showed a strong correlation with BCLC stage (p < 0.001) and total tumor diameter before treatment (p < 0.001).The GALAD score at baseline was significantly lower in patients with a 3-month response to transarterial (p > 0.001) than in refractory patients. Among patients receiving systemic treatment, the median BALAD-2 score at baseline showed a strong association with response at month 3 (p < 0.001). In the transarterial treatment group, the GALAD score (AUC = 0.715; p < 0.001) as well as the BALAD score (AUC = 0.696; p < 0.001) were associated with overall survival, hereby outperforming AFP, AFP-L3 and DCP. CONCLUSION: The GALAD score as well as the BALAD-2 score hold significant promise as a prognostic tool for patients with early or intermediate-stage HCC who are undergoing transarterial or systemic treatments.

Effect of Pre-Transplant Recipient Underweight on the Postoperative Outcome and Graft Survival in Primary Kidney Transplantation.

BACKGROUND: The objective of this study was to evaluate the influence of recipient underweight on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). PATIENTS AND METHODS: Three hundred thirty-three patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into underweight (BMI <18.5 kg/m2; N = 29) and normal weight (BMI 18.5-24.9 kg/m2; N = 304) groups. Clinicopathological characteristics, postoperative outcomes, and graft and patient survival were analyzed retrospectively. RESULTS: The postoperative rate of surgical complications and renal function were comparable between the groups. One year and 3 years after KT, 70% and 92.9%, respectively, of the pre-transplant underweight patients reached a normal BMI (≥18.5 kg/m2). The mean death-censored graft survival was significantly lower in pre-transplant underweight patients than in pre-transplant normal-weight patients (11.5 ± 1.6 years vs 16.3 ± 0.6 years, respectively; P = .045). Especially KT recipients with a moderate or severe pre-transplant underweight (BMI <17 kg/m2; N = 8) showed an increased rate of graft loss (5- and 10-year graft survival: 21.4% each). No statistical difference could be observed between the 2 groups regarding causes of graft loss. In multivariate analysis, recipient underweight (P = .024) remained an independent prognostic factor for graft survival. CONCLUSION: Being underweight did not affect the early postoperative outcome after primary KT. However, underweight, and especially moderate and severe thinness, is associated with reduced long-term kidney graft survival, and therefore this group of patients should be monitored with special attention.

Prediction of the Postoperative Outcome in Liver Resection Using Perioperative Serum Lactate Levels.

BACKGROUND: The aim of our study was to analyze perioperative lactate levels and their predictive value for postoperative mortality and morbidity after liver resection. METHODS: The clinicopathological characteristics and outcomes of 152 patients who underwent liver resection for benign and malign diagnoses were analyzed retrospectively. Lactate concentrations at three different time points, (1) before liver resection (LAC-PRE), (2) after liver resection on day 0 (LAC-POST), and (3) on day one after the operation (LAC-POD1) were assessed regarding the prognostic value in predicting postoperative complications and mortality according to the Clavien-Dindo (CD) classification. RESULTS: The rates of postoperative complications (CD ≥ IIIb) and mortality rates were 19.7% (N = 30) and 4.6% (N = 7), respectively. The LAC-PRE levels showed no correlation with the postoperative outcome. The ROC curve analysis showed that LCT-POST and LCT-POD1 values were moderately strong in predicting postoperative morbidity (0.681 and 0.768, respectively) and had strong predictive accuracies regarding postoperative mortality (0.800 and 0.838, respectively). The multivariate analysis revealed LAC-POST as a significant predictor of postoperative complications (CD ≥ IIIb: OR 9.28; 95% CI: 2.88-29.9; p < 0.001) and mortality (OR 11.69; 95% CI: 1.76-77.7; p = 0.011). CONCLUSION: Early postoperative lactate levels are a useful and easily practicable predictor of postoperative morbidity and mortality in patients after liver resection.

Rescue Allocation Modes in Eurotransplant Kidney Transplantation: Recipient Oriented Extended Allocation Versus Competitive Rescue Allocation-A Retrospective Multicenter Outcome Analysis.

BACKGROUND: Whenever the kidney standard allocation (SA) algorithms according to the Eurotransplant (ET) Kidney Allocation System or the Eurotransplant Senior Program fail, rescue allocation (RA) is initiated. There are 2 procedurally different modes of RA: recipient oriented extended allocation (REAL) and competitive rescue allocation (CRA). The objective of this study was to evaluate the association of patient survival and graft failure with RA mode and whether or not it varied across the different ET countries. METHODS: The ET database was retrospectively analyzed for donor and recipient clinical and demographic characteristics in association with graft outcomes of deceased donor renal transplantation (DDRT) across all ET countries and centers from 2014 to 2021 using Cox proportional hazards methods. RESULTS: Seventeen thousand six hundred seventy-nine renal transplantations were included (SA 15 658 [89%], REAL 860 [4.9%], and CRA 1161 [6.6%]). In CRA, donors were older, cold ischemia times were longer, and HLA matches were worse in comparison with REAL and especially SA. Multivariable analyses showed comparable graft and recipient survival between SA and REAL; however, CRA was associated with shorter graft survival. Germany performed 76% of all DDRTs after REAL and CRA and the latter mode reduced waiting times by up to 2.9 y. CONCLUSIONS: REAL and CRA are used differently in the ET countries according to national donor rates. Both RA schemes optimize graft utilization, lead to acceptable outcomes, and help to stabilize national DDRT programs, especially in Germany.

[Cholangiocarcinoma-Intrahepatic to hilar bile duct cancer]. / Cholangiokarzinome ­ intrahepatisches bis hiläres Gallengangkarzinom.

BACKGROUND: In addition to conditioning measures in liver surgery, perioperative anti-tumor therapy is becoming increasingly more important in cholangiocarcinoma (CCA). OBJECTIVE: Systematic literature review on the status of multimodal and in particular neoadjuvant therapy for CCA. MATERIAL AND METHODS: Literature overview of the current scientific original and review articles. RESULTS: Resection and rarely also liver transplantation are still the only curative treatment approaches for CCA in the non-distant metastatic stage; however, long-term results, e.g. in node positive tumors, are still unsatisfactory. Adjuvant chemotherapy is now standard but cannot be used in many patients. Neoadjuvant concepts include chemotherapy and local and locoregional procedures, such as radioembolization. Both are increasingly used in intrahepatic CCA (iCCA) but rarely in perihilar CCA. Initial data show that this is very effective in iCCA to achieve secondary operability in primarily inoperable cases. In addition, based on the current literature, neoadjuvant therapy also seems justified in operable intrahepatic CCA with a high risk of recurrence (e.g. lymph node metastases). CONCLUSION: There is a high potential for the use of multimodal therapy in CCA, which could further increase in the near future as a result of new therapeutic agents. Due to the lack of evidence clear recommendations cannot be given; however, it is becoming apparent that neoadjuvant therapy is gaining importance in iCCA and is already increasingly used as part of individual concepts in patients with a high risk of recurrence.