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European kidney donation shortages mandate efficient organ allocation by optimizing the prediction of success for individual recipients.To develop the first European online risk tool for kidney transplant outcomes on the basis of recipient-only and recipient plus donor characteristics.We used individual recipient and donor risk factors and three outcomes (death, death with functioning graft [DWFG], and graft loss) for 32 958 transplants within the Eurotransplant kidney allocation system and the Eurotransplant senior program between January 2006 and May 2018 in eight European countries to develop and validate a risk tool.Cox proportional-hazards models were used to analyze the association of risk factors with overall patient mortality, and proportional subdistribution hazard regression models for their association with graft loss and DWFG. Prediction models were developed with recipient-only and recipient-donor risk factors. Sensitivity analyses based on time-specific area under the receiver operating characteristic curve (AUC) with leave-one-country-out validation were performed and calibration plots were generated.The 10-yr cumulative incidence rate was 37% for mortality, 12% for DWFG, and 41% for graft loss. In recipient-donor models the leading risk factors for mortality were recipient diabetes (hazard ratio [HR] 10.73), retransplantation (HR 3.08 per transplant), and recipient age (HR 1.08). Effects were similar for DWFG. For graft loss, diabetes (subdistributional HR [SHR] 1.32), increased donor age (SHR 1.02), and prolonged cold ischemia time (SHR 1.02) had increased SHRs. All p values were0.001.Previously identified risk factors for outcomes following kidney transplants allow for outcome prediction with 10-yr AUC values of up to 0.81.Using European data, we estimated individual risks to predict the success of kidney transplants and support physicians in decision-making. An online tool is now available (https://riskcalc.org/ktop/) for predicting kidney transplant outcomes both before and after a donor has been identified.

Zusammenfassung Hintergrund Seit Oktober 2017 ist ein strukturiertes Entlassmanagement zur Überleitung von Patienten aus dem stationären in den ambulanten Sektor gem. § 39 Abs. 1a S. 10 SGB V gesetzlich vorgeschrieben. Umsetzung und Finanzierung obliegen dem behandelnden Krankenhaus. Ziel der Arbeit Ermittlung der Kosten des Entlassmanagements, Feststellung der Patientenzufriedenheit mit der Überleitung, Messung der Wiederaufnahmerate (Drehtüreffekt) sowie Vergleich der mittleren Krankenhausverweildauer vor und nach Einführung des Entlassmanagements in der Chirurgischen Klinik der Technischen Universität München. Methoden Einjahreskostenanalyse, retrospektive Analyse der Krankenhausverweildauer vor und nach Einführung des Entlassmanagements, Patienteninterviews zur Untersuchung der Zufriedenheit und Beurteilung der Qualität des Entlassmanagements. Ergebnisse Die Kostenanalyse ergab pauschale Kosten in Höhe von 43 € pro Patienten bzw. 391 € bei komplexem poststationären Versorgungsbedarf. Eine statistisch signifikante Verkürzung der Verweildauer durch das Entlassmanagement ließ sich in 3 Subgruppen nicht nachweisen. Die Qualität der Überleitung wurde mit Schulnoten von durchschnittlich 1,8 bis 1,9 benotet. Der Drehtüreffekt wurde bei 3,4 % der Patienten festgestellt. Diskussion Das analysierte Entlassmanagement stellt eine effektive und qualitativ erfolgreiche, jedoch kostenverursachende Maßnahme dar, die mittelfristig im Rahmen der Fallpauschalenvergütung im G‑DRG-System (German Diagnosis Related Groups) Berücksichtigung finden und voraussichtlich kostensteigernd wirken wird. Eine an die Überleitungsqualitäten der verschiedenen medizinischen Fachbereiche angepasste, fallspezifische Vergütung des Entlassmanagements könnte einen Lösungsansatz darstellen, um die Bedürfnisse verschiedener Anspruchsgruppen zu berücksichtigen.

The first-line therapy for liver malignancies is a radical extended liver resection. This high-risk operation has a high incidence of post-hepatectomy liver failure (PHLF) due to a small future liver remnant (FLR). One of the procedures to increase the FLR is the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) which is still associated with high morbidity and mortality. Here, we present a new, less invasive ALPPS variant that may be associated with lower morbidity.SoftALPPS is characterized by reduced trauma to the liver tissue and individual adaptation to the patient's health constitution. In softALPPS, portal vein embolization (PVE) is performed instead of portal vein ligation (PVL) after complete recovery of liver function. In addition, a non-absorbable foil was avoided in order to be able to extend the interval to step two or skip step two when required.Four patients successfully underwent softALPPS. Two of these patients have been followed-up for over a year (one patient with Klatskin tumor, one patient with extensive HCC). Both patients show no evidence of recurrence after 12 months and are in good medical condition. The other two patients who recently had surgery are also doing well.SoftALPPS offers the chance to curatively resect patients with high tumor burden of the liver even when the FLR is inadequate. This individual therapy method can give patients the possibility of complete tumor resection and can help to reduce perioperative morbidity.

ZUSAMMENFASSUNGDie Lebendnierenspende stellt heute angesichts des Organspendermangels eine attraktive Möglichkeit zur Transplantation eines terminal nierenkranken Patienten dar. Dennoch darf das Risiko, das der Spender durch die Operation und die anschließende Einnierigkeit eingeht, nicht außer Acht gelassen werden. Während sich der vorangegangene Artikel mit der Vorbereitung und Abklärung der Eignung des potenziellen Spenders für die Nierenlebendspende beschäftigt, thematisiert der folgende Beitrag den chirurgischen Bereich der Transplantation, gibt Einblicke in moderne Operationstechniken, benennt technische und anatomische Herausforderungen und charakterisiert die verbundenen Risiken.

ZUSAMMENFASSUNGIm Rahmen der Vorbereitung eines Lebendspenders für eine Organspende soll ein ausreichender Gesundheitszustand des Spenders dokumentiert werden, insbesondere auch hinsichtlich einer „normalen“ Nierenfunktion. Um diese richtig einzuschätzen, bedarf es einiger Überlegungen, die in diesem Beitrag erläutert werden. Zur weiteren Abklärung gehören der Ausschluss von Infektionen, Tumorerkrankungen, Herz-Kreislauf-Erkrankungen sowie Einschränkungen der Funktion der Organe oder der Psyche, die eine Lebendspende verhindern. Zusätzlich müssen immunologische Voraussetzungen (Verträglichkeitsprüfung mittels Crossmatch und die Untersuchung der Blutgruppenkompatibilität) nachgewiesen und die Vorgaben nach dem Transplantationsgesetz erfüllt werden. Vonseiten der Transplantationschirurgie gilt es dabei, möglichst früh zu klären, ob der mögliche Spender aufgrund von den bereits erwähnten Vorerkrankungen, Voroperationen oder anatomischen Gegebenheiten überhaupt für eine Spenderoperation geeignet ist. Das interdisziplinäre Team begleitet das Lebendspendenpaar in der Vorbereitungsphase eng, um alle Besonderheiten der Spender kennenzulernen und sie mit einem maximal möglichen Maß an Sicherheit zur Spende bzw. Transplantation zu führen.

ZUSAMMENFASSUNGDie Nachsorge der Lebendnierenspender kann in 3 Phasen unterteilt werden. In der postoperativen Phase, die im Wesentlichen den Klinikaufenthalt umfasst, steht das übliche postoperative Management im Vordergrund. In der Frühphase, die etwa ein Jahr andauert, werden die Weichen für die korrekte Lebensweise gestellt, Lifestyle-Modifikationen durchgeführt, die Entwicklung der Nierenfunktion überwacht und die berufliche Wiedereingliederung des Spenders einschl. psychosozialer Aspekte unterstützt. In der Langzeitphase steht weiterhin die Optimierung aller eine chronische Niereninsuffizienz begünstigenden Faktoren im Vordergrund. Zudem müssen alle Komplikationen einer selten auftretenden, aber möglichen, Nierenfunktionsverschlechterung frühzeitig erkannt und behandelt werden. Spenderinnen, die eine Schwangerschaft planen, müssen über die erhöhten Risiken erneut aufgeklärt werden. Für die jeweiligen Therapie- und Präventionsstrategien stehen die nephrologischen 1, transplantationsmedizinischen 2, 3, hypertensiologischen 4, internistischen 5 und urologischen 6 Leitlinien und Manuale 7 zur Verfügung.

Surgical strategies for chronic pancreatitis include drainage of the pancreatic duct, resection of the pancreatic head affected by inflammation, or a combination of both. These approaches aim at the elimination of pain and relief of pancreatitis-associated complications of the adjacent organs, e.g. obstruction of the biliary duct, duodenum, or portal vein. Successful outcomes yield a better quality of life for these patients. However, current data cannot clearly delineate a superior surgical method or evidence-based recommendations for the underlying aetiology of the disease or the apparent symptoms. Duodenum-preserving and partial pancreatic head resections are at least as effective and safe as the classical surgical techniques (Kausch–Whipple and pylorus-preserving Whipple) with regard to low morbidity and mortality, pain control, preservation of endocrine and exocrine function, and adequate quality of life, respectively. In long-term follow-up, operative approaches are superior to endoscopic interventions.

BackgroundThe small number of organ donors forces transplant centres to consider potentially suboptimal kidneys for transplantation. Eurotransplant established an algorithm for rescue allocation (RA) of kidneys repeatedly declined or not allocated within 5 h after procurement. Data on the outcomes and benefits of RA are scarce to date.MethodsWe conducted a retrospective 8-year analysis of transplant outcomes of RA offers based on our in-house criteria catalogue for acceptance and decline of organs and potential recipients.ResultsRA donors and recipients were both older compared with standard allocation (SA). RA donors more frequently had a history of hypertension, diabetes or fulfilled expanded criteria donor key parameters. RA recipients had poorer human leucocyte antigen (HLA) matches and longer cold ischaemia times (CITs). However, waiting time was shorter and delayed graft function, primary non-function and biopsy-proven rejections were comparable to SA. Five-year graft and patient survival after RA were similar to SA. In multivariate models accounting for confounding factors, graft survival and mortality after RA and SA were comparable as well.ConclusionsFacing relevant comorbidities and rapid deterioration with the risk of being removed from the waiting list, kidney transplantation after RA was identified to allow for earlier transplantation with excellent outcome. Data from this survey propose not to reject categorically organs from multimorbid donors with older age and a history of hypertension or diabetes to aim for the best possible HLA matching and to carefully calculate overall expected CIT.

BackgroundThe increasing organ shortage in kidney transplantation leads to the necessity to use kidneys previously considered unsuitable for transplantation. Numerous studies illustrate the need for a better decision guidance rather than only the classification into kidneys from standard or expanded criteria donors referred to as SCD/ECD-classification. The kidney donor profile index (KDPI) exhibits a score utilizing a much higher number of donor characteristics. Moreover, graft biopsies provide an opportunity to assess organ quality.MethodsIn a single center analysis 383 kidney transplantations (277 after deceased and 106 after living donation) performed between January 1st, 2006, and December 31st, 2016, retrospectively underwent SCD/ECD and KDPI scoring. Thereby, the quality of deceased donor kidneys was assessed by using the KDPI and the living donor kidneys by using the living KDPI, in the further analysis merged as (L)KDPI. Baseline biopsies taken 10 min after the onset of reperfusion were reviewed for chronic and acute lesions. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards analysis within a 5-year follow-up.ResultsThe (L)KDPI correlated with glomerulosclerosis (r = 0.30, p < 0.001), arteriosclerosis (r = 0.33, p < 0.001), interstitial fibrosis, and tubular atrophy (r = 0.28, p < 0.001) as well as the extent of acute tubular injury (r = 0.20, p < 0.001). The C-statistic of the (L)KDPI concerning 5-year death censored graft survival was 0.692. Around 48% of ECD-kidneys were classified as (L)KDPIp = 0.025). Survival analysis revealed decreased death censored (p < 0.001) and non-death censored (p < 0.001) graft survival in kidneys with an increasing (L)KDPI divided into groups of 85%, respectively.ConclusionWith a higher granularity compared to the SCD/ECD-classification the (L)KDPI is a promising tool to judge graft quality. The correlation with chronic and acute histological lesions in post-reperfusion kidney biopsies underlines the descriptive value of the (L)KDPI. However, its prognostic value is limited and underlines the urgent need for a more precise prognostic tool adopted to European kidney transplant conditions.

Discharge management has been mandatory by law in Germany since October 2017, and hospitals are required to finance and implement this. Currently there are no data available on the costs and effects of discharge management on the length of hospital stay.Determination of the costs of discharge management in the Department of Surgery at the University Hospital rechts der Isar of the Technical University of Munich, Germany, assessment of the length of stay in comparison with and without discharge management, and evaluation of patients' satisfaction to create first precedents for future negotiations about adequate financing.Cost analysis of discharge management in the Department of Surgery at the School of Medicine at the Technical University of Munich, retrospective analysis of the mean length of hospital stays before and after implementation of discharge management, and patient surveys on the quality of the structured transition process and their satisfaction.The cost analysis revealed lump costs of € 43 per patient and € 391 for patients with a need for complex management. No statistically significant shorter length of hospital stay after the implementation of discharge management was found by analyzing three patient subgroups. The overall rate of patients returning to the hospital due to complications associated with the surgical procedure was 3.4%.Discharge management in the Department of Surgery at the hospital is an effective and potentially quality-enhancing but at the same time cost-driving measure, which, in the medium term, will enter G‑DRG rates and may thus increase costs. A possible solution to meet various stakeholders' needs could be a case-specific financial remuneration of discharge management that is adapted to the transition qualities of the various medical departments.HINTERGRUND: Seit Oktober 2017 ist ein strukturiertes Entlassmanagement zur Überleitung von Patienten aus dem stationären in den ambulanten Sektor gem. § 39 Abs. 1a S. 10 SGB V gesetzlich vorgeschrieben. Umsetzung und Finanzierung obliegen dem behandelnden Krankenhaus.Ermittlung der Kosten des Entlassmanagements, Feststellung der Patientenzufriedenheit mit der Überleitung, Messung der Wiederaufnahmerate (Drehtüreffekt) sowie Vergleich der mittleren Krankenhausverweildauer vor und nach Einführung des Entlassmanagements in der Chirurgischen Klinik der Technischen Universität München.Einjahreskostenanalyse, retrospektive Analyse der Krankenhausverweildauer vor und nach Einführung des Entlassmanagements, Patienteninterviews zur Untersuchung der Zufriedenheit und Beurteilung der Qualität des Entlassmanagements.Die Kostenanalyse ergab pauschale Kosten in Höhe von 43 € pro Patienten bzw. 391 € bei komplexem poststationären Versorgungsbedarf. Eine statistisch signifikante Verkürzung der Verweildauer durch das Entlassmanagement ließ sich in 3 Subgruppen nicht nachweisen. Die Qualität der Überleitung wurde mit Schulnoten von durchschnittlich 1,8 bis 1,9 benotet. Der Drehtüreffekt wurde bei 3,4 % der Patienten festgestellt.Das analysierte Entlassmanagement stellt eine effektive und qualitativ erfolgreiche, jedoch kostenverursachende Maßnahme dar, die mittelfristig im Rahmen der Fallpauschalenvergütung im G‑DRG-System (German Diagnosis Related Groups) Berücksichtigung finden und voraussichtlich kostensteigernd wirken wird. Eine an die Überleitungsqualitäten der verschiedenen medizinischen Fachbereiche angepasste, fallspezifische Vergütung des Entlassmanagements könnte einen Lösungsansatz darstellen, um die Bedürfnisse verschiedener Anspruchsgruppen zu berücksichtigen.

Delayed graft function (DGF) following kidney transplantation is associated with increased risk of graft failure, but biomarkers to predict DGF are scarce. We evaluated serum uromodulin (sUMOD), a potential marker for tubular integrity with immunomodulatory capacities, in kidney transplant recipients and its association with DGF. We included 239 kidney transplant recipients and measured sUMOD pretransplant and on postoperative Day 1 (POD1) as independent variables. The primary outcome was DGF, defined as need for dialysis within one week after transplantation. In total, 64 patients (27%) experienced DGF. In multivariable logistic regression analysis adjusting for recipient, donor and transplant associated risk factors each 10 ng/mL higher pretransplant sUMOD was associated with 47% lower odds for DGF (odds ratio (OR) 0.53, 95% confidence interval (95%-CI) 0.30–0.82). When categorizing pretransplant sUMOD into quartiles, the quartile with the lowest values had 4.4-fold higher odds for DGF compared to the highest quartile (OR 4.41, 95%-CI 1.54–13.93). Adding pretransplant sUMOD to a model containing established risk factors for DGF in multivariable receiver-operating-characteristics (ROC) curve analysis, the area-under-the-curve improved from 0.786 [95%-CI 0.723–0.848] to 0.813 [95%-CI 0.755–0.871, p = 0.05]. SUMOD on POD1 was not associated with DGF. In conclusion, higher pretransplant sUMOD was independently associated with lower odds for DGF, potentially serving as a non-invasive marker to stratify patients according to their risk for developing DGF early in the setting of kidney transplantation.

ZUSAMMENFASSUNGDie Nierentransplantation stellt heute – mehr als ein halbes Jahrhundert nach ihrer Einführung in die klinische Behandlung – ein etabliertes und sicheres Therapieverfahren mit guten Langzeitergebnissen dar. Sie führt im Vergleich zur Dialyse zu einer Verbesserung der Lebensqualität und Reduktion der Mortalität. Das Patienten- und Transplantatüberleben konnten in den letzten Jahrzehnten stetig verbessert werden. Das 5-Jahres-Transplantatüberleben nach Nierentransplantation beträgt nach postmortaler Spende 74 % bzw. nach Lebendspende 86 % 1. Demgegenüber steht aber ein zunehmender Mangel an Spenderorganen, der in Deutschland und im gesamten Eurotransplant-Bereich zu einer zunehmend offensiven Nutzung von Organangeboten mit sogenannten erweiterten Spenderkriterien (ECD: „extended criteria donor“) geführt hat. Im Vergleich zu Standardkriterien für Spendernieren („standard criteria donor“) sind ECD-Nieren mit einem bis zu 2-fach erhöhten Risiko für eine verzögerte Transplantatfunktion, akute Abstoßung und einen Transplantatverlust verbunden. Voraussetzungen für eine langfristig erfolgreiche Transplantation der ECD-Transplantate waren und sind v. a. grundlegende Kenntnisse der Immunologie zur Vermeidung von Abstoßungsreaktionen.

PURPOSE OF REVIEW Organ shortage forces those responsible to streamline allocation rules to provide a maximum of candidates with a graft and to optimize transplant outcome. Recently, repeated kidney re-transplantation was investigated in several studies with different analytic settings concerning the control group, the donors, parameters influencing outcome, and demographic characteristics. This review gives an overview on the candidates awaiting a repeated re-transplantation, summarizes the outcome, and comments on the relevance of these findings in the context of sustained organ shortage. RECENT FINDINGS Repeated kidney re-transplantation is technically and immunologically feasible and the recipients' survival is better compared to candidates remaining on dialysis or on the waiting-list. However, the outcome is mainly reported to be worse as compared to first or second kidney transplantation. Kidneys from living donors seem to have a favorable impact on outcome in this setting. SUMMARY The survival benefit of repeated re-transplantation recipients over patients on dialysis demands for continuation of this procedure. Comprehensive registries are essential to continuously optimize allocation. Governmental authorities are obliged to set the course to increase organ donation rather than forcing transplant decision makers to withhold a third or fourth graft from any candidate.

Between 2007 and 2016, 140 consecutive patients who underwent resection of colorectal cancer with simultaneous liver metastases at a single university hospital were retrospectively analysed. In order to gather information regarding potential survival differences for n = 68 simultaneous versus n = 72 staged resections of the colorectal primary tumor and the liver metastases, Clinical, histopathological, serological, and survival data were compared for those two patient groups. The rate of simultaneous tumor resections increased from approximately 25% in 2007 to >75% in 2016. There was no difference in tumor specific survival for patients with simultaneous vs. staged resection (p = 0.631). This effect continued after excluding patients with extrahepatic metastases (p = 0.440). Further, neoadjuvant treatment did not lead to differences in the tumor-specific survival (p = 0.123). Factors associated with an increased tumor-specific survival were low ASA score (p

For patients with colorectal cancer and synchronous liver metastasis, either a simultaneous, or a two-staged resection of the primary tumor and the liver metastases is possible. There are currently no guidelines preferring one approach to the other.Consecutive patients who underwent hepatic resection at our university hospital from 2007-2016 were included. Clinical, histopathologic, serologic, and survival data were analyzed. The primary end point was tumor-specific survival for patients with simultaneous versus staged resections.Of all 140 patients, 68 underwent simultaneous resection and 72 underwent staged resection. The characteristics of both groups were comparable. Patients with simultaneous resections had a shorter duration of cumulative operation time (299 versus 460 min; P = 0.003) and a shorter cumulative length of hospital stay (23 versus 43 d; P = 0.002). Perioperative mortality (P = 0.257) did not differ significantly; however, patients with simultaneous resections had higher rates of grade 2 complications according to Clavien-Dindo (P 0.001). Tumor-specific 1-y survival was 85 ± 5% for simultaneous and 83 ± 5% for staged resection (P = 0.631). On multivariable analysis, pT4 (P = 0.038), pN3 (P = 0.003), and G3/4 (P = 0.041) of the primary tumor and postoperative complications (Clavien-Dindo 3/4/5, P = 0.003) were poor prognostic factors regarding tumor-specific survival.This is one of the largest and most thoroughly documented retrospective single-center studies of consecutive patients with synchronous hepatic metastases. Simultaneous resection of colorectal cancer together with hepatic metastases is a safe procedure in selected patients and does not have a significant influence on long-term survival.

Transplant international (2020). doi:10.1111/tri.13569, Published by Wiley-Blackwell, Oxford [u.a.]

ZusammenfassungDie antikörpervermittelte Abstoßung nach einer Nierentransplantation mit dem Nachweis von (de novo) donorspezifischen HLA-Antikörpern gehört derzeit zu den größten Herausforderungen bei der Nierentransplantation. Ungeklärt bleiben letztlich die Bedeutung von Persistenz oder Verlust der donorspezifischen Antikörper und wie die Therapie bei gefährdeten Patienten aussehen sollte. Wer sollte zu welchem Zeitpunkt und mit welchem Medikamentenprotokoll eine Desensibilisierung erhalten? In dieser Übersicht werden diagnostische und therapeutische Verfahrensweisen bezüglich der antikörpervermittelten Abstoßung und bei hochimmunisierten Patienten bei Nierentransplantation dargestellt und Strategien zur Vermeidung einer antikörpervermittelten Rejektion aufgezeigt.

ZusammenfassungIn Zeiten anhaltend niedriger Organspendezahlen müssen neue Wege in der Allokation von Nierentransplantaten gegangen werden. Notwendig ist dies zum einen, um aus dem dramatisch angespannten Spenderpool ein Maximum an Transplantationen zu erzielen, die darüber hinaus auch langfristig ein gutes Transplantat-Outcome aufweisen sollen. Zum anderen gilt es, eine frühzeitige Wiederaufnahme des Empfängers auf die Warteliste wegen des Verlusts des Transplantats zu vermeiden. Eurotransplant hat inzwischen vielfältigen Allokationswege von Nierentransplantaten etabliert, unter anderem die sogenannte „High-urgency“-Nierentransplantation, die es aufgrund aktueller Studienergebnisse vor dem Hintergrund des Organspendermangels medizinisch, ethisch und gesundheitspolitisch neu zu bewerten gilt

Der Goldstandard der Immunsuppression nach Nierentransplantation gemäß aktuellen KDIGO-Empfehlungen 1 besteht nach wie vor aus einem Calcineurininhibitor (CNI), Mycophenolsäure und Steroiden – der sog. Tripel-Therapie. Der große Durchbruch in der Langzeitüberlebensrate von Nierentransplantaten gelang erst in den 1990er-Jahren mit dem Einsatz von Ciclosporin A. Mit Einführung des ähnlich wirkenden, aber potenteren Tacrolimus 2 wurde dieser CNI in die Empfehlungen der KDIGO als Erstlinienpräparat in der de novo Immunsuppression aufgenommen 1. Vonseiten des Nebenwirkungsprofils zeigen die CNI jedoch unerwünschte Nebenwirkungen wie z. B. Nephrotoxizität, die im Rahmen der sog. CNI-Toxizität die Transplantatlangzeitfunktion einschränken und limitieren kann. Darüber hinaus findet sich ein erhöhtes Risiko für Hypertonie, Fettstoffwechselstörungen und insbesondere für Tacrolimus die Auslösung eines Post-Transplantations-Diabetes (NODAT: New Onset Diabetes After Transplantation) oder Aggravierung eines bestehenden Diabetes mellitus.

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a nuclear receptor demonstrated to play an important role in various biological processes. The aim of this study was to determine the effect of PPARγ on liver regeneration upon partial hepatectomy (PH) in mice. Mice were subjected to two-thirds PH. Before surgery, mice were either treated with the PPARγ agonist rosiglitazone, the PPARγ antagonist GW9662 alone, or with the c-met inhibitor SGX523. Liver-to-body-weight ratio, lab values, and proliferation markers were assessed. Components of the PPARγ-specific signaling pathway were identified by western blot and qRT-PCR. Our results show that liver regeneration is being inhibited by rosiglitazone and accelerated by GW9662. Inhibition of c-Met by SGX523 treatment abrogates GW9662-induced liver regeneration and hepatocyte proliferation. Hepatocyte growth factor (HGF) protein levels were significantly downregulated after rosiglitazone treatment. Activation of HGF/c-Met pathways by phosphorylation of c-Met and ERK1/2 were inhibited in rosiglitazone-treated mice. In turn, blocking phosphorylation of c-Met significantly abrogated the augmented effect of GW9662 on liver regeneration. Our data support the concept that PPARγ abrogates liver growth and hepatocellular proliferation by inhibition of the HGF/c-Met/ERK1/2 pathways. These pathways may represent potential targets in response to liver disease and could impact on the development of molecular therapies.

Pylorus-preserving partial pancreaticoduodenectomy is considered to be one of the most demanding and comprehensive operative procedures in visceral surgery and is usually performed for malignant lesions of the pancreatic head, the distal bile duct, or the duodenum. Numerous modalities of this procedure, which can be structurally divided into exploration, resection, and reconstruction, have been defined. The particularly determining relevance of postoperative pancreatic fistulas probably causes the outstanding key role of the pancreatic (duct) anastomosis during the procedure, which led to multitudinous clinical and experimental studies aiming for the best anastomotic technique. This chapter describes the procedure of the pylorus-preserving pancreaticoduodenectomy as performed at our center, illustrates the distinct operative phases with detailed pictures, and puts special emphasis on both the pancreatic and the biliodigestive anastomoses with clear drawings.

Seit der Einfuhrung der Nierentransplantation in Deutschland vor uber 30 Jahren ist die Zahl der Langzeittransplantierten und damit das Tumorrisiko fur die Empfanger gestiegen. Tumorgenese und Tumorinzidenzen werden insbesondere unter dem Aspekt der Langzeitimmunsuppression untersucht. Notwendige Screening-Verfahren und Risikofaktoren bei den einzelnen Tumortypen werden analysiert, sowie Therapieempfehlungen untersucht. Im Gesprach mit dem Patienten ist der Verlust der Lebensqualitat mit einem moglichen Transplantatverlust unter der Therapie gegenuber der Lebenserwartung zu erortern.

Im Szenario der Nierentransplantation lassen sich durch eine verbesserte immunologische Diagnostik (hoch) immunisierte Patienten zunehmend identifizieren. In diesem Beitrag wird der aktuelle Stand in Diagnostik und Therapie dieser Patientengruppe analysiert und es werden die Grenzen derzeitiger Therapieansatze dargestellt.

Background Activation of the immune system in terms of subseptic conditions during liver regeneration is of paramount clinical importance. However, little is known about molecular mechanisms and their mediators that control hepatocyte proliferation. We sought to determine the functional role of immune cells, especially NKT cells, in response to partial hepatectomy (PH), and to uncover the impact of the integrin lymphocyte function-associated antigen-1 (LFA-1) on liver regeneration in a subseptic setting. Methods Wild-type (WT) and LFA-1-/- mice underwent a 2/3 PH and low-dose lipopolysaccharid (LPS) application. Hepatocyte proliferation, immune cell infiltration, and cytokine profile in the liver parenchyma were determined. Results Low-dose LPS application after PH results in a significant delay of liver regeneration between 48h and 72h, which is associated with a reduced number of CD3+ cells within the regenerating liver. In absence of LFA-1, an impaired regenerative capacity was observed under low-dose LPS application. Analysis of different leukocyte subpopulations showed less CD3+NK1.1+ NKT cells in the liver parenchyma of LFA-1-/- mice after PH and LPS application compared to WT controls, while CD3-NK1.1+ NK cells markedly increased. Concordantly with this observation, lower levels of NKT cell related cytokines IL-12 and IL-23 were expressed in the regenerating liver of LFA-1-/- mice, while the expression of NK cell-associated CCL5 and IL-10 was increased compared to WT mice. Conclusion A subseptic situation negatively alters hepatocyte proliferation. Within this scenario, we suggest an important impact of NKT cells and postulate a critical function for LFA-1 during processes of liver regeneration.

We investigated the applicability of both Acute Physiology And Chronic Health Evaluation II (APACHE II) and Mannheim Peritonitis Index (MPI) in transplant recipients with intestinal perforation as polymicrobial peritonitis is highly life-threatening in patients with impaired immunological defence and the course of abdominal sepsis is aberrant compared to non-immunosuppressed individuals. In a retrospective database analysis, we validated the consistency of APACHE II and MPI in death prediction in septic peritonitis. In a matched-pair analysis we then investigated their applicability in immunosuppressed transplant recipients. The validation of the scores was performed with 125 non-immunosuppressed patients. In a matched-pair analysis 16 immunosuppressed transplant recipients were compared with 32 controls. In accordance with clinical observations, statistical analyses revealed significantly higher MPI scores in immunosuppressed transplant recipients (P = 0.0007), whereas APACHE II scores were comparable. Linear regression analysis revealed that predicted death rates derived from APACHE II and MPI differ significantly (P = 0.0344) in immunosuppressed transplant recipients compared to controls. Both scores consistently serve as reliable tools for prediction of lethality in septic peritonitis but they fail in immunosuppressed organ recipients. Our findings clearly confirm that in immunosuppressed patients severe peritonitis might be present despite an a- or oligosymptomatic clinical course.

Das hepatorenale Syndrom ist ein von zahlreichen Faktoren beeinflusstes Syndrom im Rahmen einer fortgeschrittenen Hepatopahie mit dem Leitsymptom eines haufig oligurischen Nierenversagens sowie Aszites. Eine zentrale Rolle spielt die arterielle Vasodilatation im Splanchnikusstromgebiet mit der Folge eines Poolings und einem konsekutiv verminderten effektiv zirkulierenden Blutvolumen. Wahrend die Vasodilatation durch Substanzen wie NO, aber auch CGRP, Substanz P, CO, Endocannabinoide und Adrenomedullin induziert wird und das Fassungsvermogen der Strombahn durch Bildung von Varizen und Kollateralen durch Stimulation uber VEGF und PDGF zunimmt, kommt es zu einer Gegenregulation in den anderen Stromgebieten. Durch eine Aktivierung des RAAS, eine Stimulation der Barorezeptoren an den Karotiden, die Freisetzung von Vasopressin und die Aktivierung des Sympathikus kommt es zu einer intensiven Vasokonstriktion der Aa. renales mit einer reduzierten glomerularen Filtrationsrate. Hier fehlen beim hepatorenalen Syndrom zusatzlich lokal vasodilatativ wirkende renale Prostaglandine. Der Organismus kann in der fruhen Phase eines hepatorenalen Syndroms noch insbesondere uber das Herz-Zeit-Volumen eine zusatzliche Kompensation aufrechterhalten – ein Pathomechanismus, der jedoch langfristig durch die zirrhotische Kardiomyopathie begrenzt wird. Der vulnerable Organismus eines Patienten mit hepatorenalem Syndrom kann durch exogene Storfaktoren an zahlreichen Positionen so getroffen werden, dass es zu einer rapiden Entgleisung und Dekompensation kommen kann.

Das hepatorenale Syndrom ist ein funktionelles Nierenversagen bei akuter oder chronischer Leberinsuffizienz. Der Zusammenhang zwischen Nierenversagen und Leberzirrhose wurde 1861 durch Freirichs und 1863 durch Flint das erste Mal beschrieben. Beim HRS Typ 1 verschlechtert sich die Nierenfunktion innerhalb weniger Tage, beim hepatorenalen Syndrom Typ 2 ist die Nierenfunktion auf einem stabilen Niveau eingeschrankt. Die Diagnose des HRS basiert auf dem Ausschluss anderer konkurrierender Ursachen fur das Nierenversagen. Die Therapie des hepatorenalen Syndroms beruht auf der Korrektur des Saure-Basen-Haushalts, Transfusion bei Anamie, intravenoser Gabe von Albumin, Parazentese sowie Vermeidung von nephrotoxischen Substanzen. Gezielte medikamentose Therapien oder die Anlage eines transjugularen intrahepatischen portosystemischen Shunts konnen eine Optimierung der Nierenfunktion bewirken. Eine kombinierte Leber-Nieren-Transplantation ist nur bei einer irreversiblen parenchymatosen Nierenerkrankung indiziert.

Exposure to heparin is associated with a high incidence of immunization against platelet factor 4 (PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia (HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on anti-heparin/PF4 antibodies and HIT in transplant recipients a systematic PubMed literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far.

Item does not contain fulltext BACKGROUND: In the Eurotransplant Kidney Allocation System (ETKAS), transplant candidates can be considered for high-urgency (HU) status in case of life-threatening inability to undergo renal replacement therapy. Data on the outcomes of HU transplantation are sparse and the benefit is controversial. METHODS: We systematically analysed data from 898 ET HU kidney transplant recipients from 61 transplant centres between 1996 and 2010 and investigated the 5-year patient and graft outcomes and differences between relevant subgroups. RESULTS: Kidney recipients with an HU status were younger (median 43 versus 55 years) and spent less time on the waiting list compared with non-HU recipients (34 versus 54 months). They received grafts with significantly more mismatches (mean 3.79 versus 2.42; P < 0.001) and the percentage of retransplantations was remarkably higher (37.5 versus 16.7%). Patient survival (P = 0.0053) and death with a functioning graft (DwFG; P < 0.0001) after HU transplantation were significantly worse than in non-HU recipients, whereas graft outcome was comparable (P = 0.094). Analysis according to the different HU indications revealed that recipients listed HU because of an imminent lack of access for dialysis had a significantly worse patient survival (P = 0.0053) and DwFG (P = 0.0462) compared with recipients with psychological problems and suicidality because of dialysis. In addition, retransplantation had a negative impact on patient and graft outcome. CONCLUSIONS: Facing organ shortages, increasing wait times and considerable mortality on dialysis, we question the current policy of HU allocation and propose more restrictive criteria with regard to individuals with vascular complications or repeated retransplantations in order to support patients on the non-HU waiting list with a much better long-term prognosis.

We investigated the prevalence of HIT II in liver transplant recipients and analysed associated factors. In recipients with clinically suspected HIT II in the 4Ts pretest clinical scoring system HIPA-assay was performed. Next, 37 clinical variables were analysed retrospectively for their association with HIT II. Factors significantly correlated to our findings in univariate analysis were included in a multivariate model and binary logistic regression analysis. Among 46 recipients 21 patients were suspicious in the 4Ts pretest and 14 of them (30.4%) were diagnosed HIT-antibody positive. Patient's age (P = 0.001), postoperative dialysis (P = 0.028), and postoperative hospital stay (P = 0.035) were significantly associated with development of HIT-antibodies in univariate analysis. Postoperative dialysis and postoperative hospital stay turned out as epiphenomena of patient's age, the only independent predictor (P = 0.021). Using multiple χ(2) -testing, a cut-off could be calculated, assigning patients younger than 59 years to a low risk group and patients of 59 years and older to a high risk group. High incidence of peri-operative HIT II seroconversion in liver transplant recipients is not associated with factors known to induce thrombocyte activation, like blood products or cell-saver. Only patients' age was identified as independent predictor.

BACKGROUND: Rat liver transplantation is a common method in liver transplantation research. There are lots of different methods described until today. Although liver transplantation with retrograde reperfusion is established in the clinical routine there is no rat liver model described. METHODS: Arterialized rat liver transplantation with initial retrograde reperfusion was performed on n = 7 male LEWIS-(RT1)-rats. 1, 24 and 48 hours after the operation, serum parameters were determined. Furthermore, after 48 hours the liver was taken for histological assessment. RESULTS: The AST and the ALT levels showed a linear decrease during the first 48 hours after transplantation. GLDH levels showed an increase during the first 24 hours before they decreased strongly. In histology, the livers showed a good quality with only less necrosis. The highest amount of necrosis could be seen in the Rappaport zone 3. CONCLUSIONS: We were able to show that arterialized rat liver transplantation with initial retrograde reperfusion is feasible and shows a good outcome. Especially in centers where retrograde reperfusion of the liver is performed in clinical transplantation this method should be used for transplantation research to reach the closest possible relation between science and clinic.

Palliative treatment concepts are considered in patients with non-curatively resectable and/or metastasized pancreatic cancer. However, patients without metastases, but presented with marginally resectable or locally non-resectable tumors should not be treated by a palliative therapeutic approach. These patients should be enrolled in neoadjuvant radiochemotherapy trials because a potentially curative resection can be achieved in approximately one-third of them after finishing treatment and restaging. Within the scope of best possible palliative care, resection of the primary cancer together with excision of metastases represents a therapeutic option to be contemplated in selected cases. Comprehensive palliative therapy is based on treatment of bile duct or duodenal obstruction for certain locally unresectable or metastasized advanced pancreatic cancer. However, endoscopic or percutaneous stenting procedures and surgical bypass provide safe and highly effective therapeutic alternatives. In case of operative drainage of the biliary tract (biliodigestive anastomosis), the prophylactic creation of a gastro-intestinal bypass (double bypass) is recommended. The decision to perform a surgical versus an endoscopic procedure for palliation depends to a great extent on the tumor stage and the estimated prognosis, and should be determined by an interdisciplinary team for each patient individually.

Die Ergebnisse nach simultaner Nieren-Pankreas-Transplantation (NPTx) und nach orthotoper Lebertransplantation (LTx) haben sich die letzten Jahre nicht zuletzt dank moderner Immunsuppression verbessert. Inzwischen gehort die NPTx zur etablierten Therapie bei Patienten mit Typ-I-Diabetes und terminaler Niereninsuffizienz. Patienten nach erfolgreicher NPTx haben nicht nur eine hohere Lebenserwartung, sondern auch eine bessere Lebensqualitat. Nach NPTx liegen die 1-Jahres-Transplantatuberlebensraten >85%, Abstosungsraten

Effective immunosuppressive therapy is essential to prevent transplant rejection but renders patients vulnerable to opportunistic infections. The present study investigates the effects of common immunosuppressive drugs on the course of septic peritonitis in an experimental mouse model. We show that treatment with a combination of tacrolimus, mycophenolate mofetil, and methylprednisolone resulted in highly elevated lethality of septic peritonitis. When immunosuppressive drugs were combined with antibiotic therapy, however, mice were almost completely protected. The combination of mycophenolate mofetil and methylprednisolone was shown to be required and sufficient to improve outcome of septic peritonitis in the presence of antibiotic therapy. Combined immunosuppressive and antibiotic therapy, but not antibiotic therapy alone, resulted in enhanced bacterial clearance. These beneficial effects were linked to an elevated expression of activation markers and an increased production of reactive oxygen metabolites by peritoneal neutrophils and correlated with a reduced messenger RNA expression of the inhibitory cytokine IL-22. In contrast, systemic or peritoneal levels of IL-10, IL-12, TNF-alpha, keratinocyte chemoattractant, and monocyte chemoattractant protein 1, and splenic messenger RNA levels of IFN-gamma were not influenced by the immunosuppressive therapy. These results therefore suggest that combined immunosuppressive and antibiotic therapy may improve bacterial clearance and survival of septic peritonitis by a mechanism that involves enhanced activation and antimicrobial activity of neutrophils and reduced production of IL-22.