Objective: The purpose of the present study was to explore the platelet function during the perioperative period of orthotopic liver transplantation (OLT) due to the underlying liver disease.Methods: The blood coagulation parameters, platelet surface markers and the determination of platelet aggregation were analyzed in 34 patients who underwent OLT. Blood samples were drawn preoperatively, anhepatic, 10 min and 1 hour after reperfusion, 1 day, 3 and 7 days postoperatively. Conventional coagulation screens, thrombopoietin (TPO) serum levels, P-selectin, GPIIb/IIIa and GPIb binding sites on the surface of platelets as evaluated by flow cytometry and platelet aggregation response were measured.Results: Coagulation factors, maximum aggregation and rate of aggregation were significantly different before transplantation due to the underlying liver disease. Further we found a markedly depressed GPIIb/IIIa and P-selectin expression and a reduced rate of aggregation in all patients throughout the study. In contrast maximum aggregation of platelets was restored on the third day after reperfusion without intergroup differences and almost comparable to healthy controls. An inverse correlation was found between peripheral platelet count pre-transplantation and peak TPO concentrations one weak post-transplantation.Conclusions: In the entire process of OLT, coagulation factors, maximum aggregation and rate of platelet aggregation depend on the surgical phases during transplantation and on the underlying liver disease. The data obtained in this study might contribute to a better understanding of the pathophysiology and assessment of bleeding risk in OLT. (C) 2009 Elsevier Ltd. All rights reserved.

Background: Hemodialysis patients are in a state of oxidant stress. In renal transplantation reactive oxygen species (ROS) are considered to be important factors of ischemia-reperfusion injury. Neutrophils produce ROS as part of the host defense against invading bacteria. This study was designed to investigate whether neutrophil function in hemodialysis patients is immediately affected by renal transplantation. Methods: We evaluated the neutrophil respiratory burst and phagocytic activity in renal transplant patients with living-related donor (LRD) and cadaveric donor (CAD) grafts using flow cytometry techniques. Twenty patients (LRD = 6, CAD = 14) and 20 healthy volunteers were included in the study. Venous blood samples were drawn before anesthesia, 5 min before reperfusion, 1 h and 1, 3 and 7 days after reperfusion. Results: Before surgery, a significant increase in hydrogen peroxide production in neutrophils was seen for both renal transplantation groups compared to healthy subjects. Within 24 h after reperfusion hydrogen peroxide production almost decreased to normal values. The phagocytic capacity of neutrophils was continuously depressed. There were no differences between the CAD and LRD groups. Conclusions: We found that the enhanced respiratory burst activity of patients with chronic renal failure decreased to normal values within 1 day following renal transplantation. Our results suggest that reduced respiratory burst activity resulting in a diminished risk of tissue damage by the uncontrolled production of ROS.

Platelet dysfunction contributes to haemostatic defects, possibly leading to bleeding complications. We hypothesised that liver transplantation and liver resection, together with portal clamping time, might be a potential stimulus for platelet activation. Therefore, we determined the expression of platelet GPIIb/IIIa and P-selectin, representing important platelet activation markers, and the thrombopoietin (TPO) serum level after transplantation and resection. Twenty patients [ten that had undergone orthotopic liver transplantation (OLT), ten with liver resection (LRX)] were included in the study. From sequential venous blood samples, surface expression of GPIIb/IIIa and P-selectin was quantified by flow cytometry, and TPO serum levels were determined by ELISA. Baseline GPIIb/IIIa receptor expression on circulating platelets was significantly reduced in the OLT group compared to the LRX group and healthy volunteers. GPIIb/IIIa expression after activation with TRAP-6 increased significantly ( P <0.001) in the LRX group but not in the OLT group. P-selectin expression after TRAP-6 stimulation increased significantly ( P <0.001) in the LRX group, being comparable to that in healthy volunteers, whereas only a very low increase in the OLT group was found. In the OLT group, TPO serum levels were in the lower normal range and rose above the upper limit of normal values 24 h after reperfusion. These data indicate that neither liver transplantation nor liver resection influences GPIIb/IIIa and P-selectin expression on circulating platelets. There was a lack of expression in cirrhotic patients and unimpaired baseline expression and functional reserve in non-cirrhotic liver-resection patients. After liver transplantation, increasing serum TPO levels, which indicated a recovering graft function, resulted in rising peripheral platelet counts.

We have investigated the effect of dopamine and dopexamine on the isolated perfused rat kidney. After an equilibration period of 20 min and two control periods of 10 min, dopexamine 1.0, 2.5 or 4.0 micrograms kg-1 min-1 or dopamine 2.0 micrograms kg-1 min-1 were perfused for a further 40 min in random order. Renal blood flow, urine volume, glomerular filtration rate, absolute sodium excretion and fractional sodium reabsorption of the isolated perfused kidney were measured every 10 min during the experiment. Dopamine increased significantly urine production from mean 61.54 (SEM 4.7) to 117.2 (9.7) microliters min-1 g-1 and absolute sodium excretion from 0.4 (0.1) to 1.2 (0.1) mumol min-1 g-1, and decreased significantly fractional sodium reabsorption from 97.3 (0.5) to 90.7 (0.7)%. Renal blood flow and glomerular filtration rate were not altered. In contrast, dopexamine had no effect on the isolated kidney. These data suggest that the diuretic and natriuretic effects of dopexamine in humans may not result from a direct action on the kidney.

A case of unresectable liver metastases in a patient with breast cancer is reported. Isolated abdominal perfusion chemotherapy was performed in the patient, a 48-year old woman who complained of severe abdominal pain despite receiving analgetic treatment. The perfusion was uneventful, but 3h later the patient showed dilated and light-fixed pupils. A cranial computed tomography scan revealed a massive intracerebral hemorrhage and intracerebral metastasis. Brain death developed and the patient died 26h after stop-flow perfusion. Based on this experience, any intracerebral metastasis should be considered as a contraindication for abdominal and pelvic stop-flow chemoperfusion.

The present study investigated the pathophysiology of primary nonfunction (PNF) of grafted livers with regard to hepatic tissue oxygenation. Hemoglobin oxygen saturation in hepatic tissue (H−So2) after reperfusion was determined using near-infrared spectroscopy. Graft tissue oxygen consumption was also estimated according to Fick's principle. Six grafts with PNF were compared with 40 functioning grafts. One PNF graft with extremely low and heterogenous H−So2 after reperfusion was found to contain multiple intrahepatic portal thrombi. However, five other PNF grafts showed no lower and, on the contrary, more homogeneous H−So2 at the end of the operation. As a whole, mean H−So2 was negatively correlated and the coefficient of variation (CV) of H−So2 was positively correlated with graft tissue oxygen consumption at the end of the operation; grafts whose H−So2 showed a secondary decrease had better initial function. In later relaparotomy, the H−So2 of the five PNF grafts was significantly higher and more homogeneous than that of the functioning grafts. These results suggest that the H−So2 level reflects tissue oxygen consumption as well as oxygenation, and that the dissociation of both factors can occur in hepatic graft reperfusion. Not only low and heterogeneous H−So2 but also high and homogenous H−So2, suggesting some shunt mechanism, can be signs of poor graft function.

In this study we investigated three groups of patients, the first undergoing liver transplantation (n = 9), the second resection of the liver (n = 7) and the third cardiac surgery (n = 10) with regard to changes of ionized and total magnesium concentration during operation. Liver transplantation: Ionized magnesium concentration decreased from 0.58 mmol/L to 0.34 mmol/L far below the reference interval (0.49-0.72 mmol/L), whereas total magnesium concentration changed only from 0.78 mmol/L to 0.67 mmol/L (reference interval: 0.65-1.05 mmol/L). Citrate concentration increased from 220 mumol/L to 1925 mumol/L (anhepatic stage) because of massive transfusion of blood products. It was inversely correlated to ionized magnesium concentration. Resection of the liver: There was a decline of ionized magnesium from 0.56 mmol/L to 0.43 mmol/L, which slightly exceeded the decline of total magnesium from 0.74 mmol/L to 0.64 mmol/L. Citrate concentration increased moderately even in cases, when no citrate was administered reflecting reduced hepatic function during operation. Cardiac surgery: Only in patients, to whom citrate but not magnesium was infused, ionized magnesium concentration fell slightly below the reference interval (0.45 mmol/L). In the other patients, to whom magnesium was administered, ionized magnesium concentration was within the reference interval or exceeded it. It is concluded that in patients with impaired hepatic function and/or high citrate load the monitoring of ionized magnesium concentration is mandatory.

Resection remains the treatment of choice in liver cancer. In order to avoid liver transplantation in conventionally unresectable tumors ex-situ (“bench” procedure), in-situ and ante-situm resection technique should be prefered whenever feasible. Despite the deficiency of donor organs, a single center experience with 198 patients reveals that liver transplantation continues its role as a therapeutic option for selected patients. At present “favorable” indications for transplantation are International Union against Cancer (UICC)-stage II hepatocellular carcinoma as well as the subtype fibrolamellar carcinoma, uncommon tumors such as epitheloid hemangioendothelioma, hepatoblastoma, and liver metastases from neuroendocrine tumors. Due to unsatisfying results, intrahepatic bile duct-, stage III and IV hepatocellular carcinoma, hemangiosarcoma, and liver metastases from nonendocrine primaries should be excluded from liver transplantation alone. For these advanced tumors, especially in cases of extrahepatic involvement, a combination of liver transplantation and multivisceral resection has been proven feasible. However, a significant improvement in patient survival may only be expected by currently investigated multimodality treatment protocols which will require further randomized studies.

Nach Lebertransplantation zeigt die Mehrzahl der Transplantate einen mehr oder weniger ausgeprägten Ischämieschaden, bedingt durch unterschiedlichste Faktoren, wie z.B. Spenderauswahl, Organentnahme einschl. Perfusions- und Konservierungstechniken, Ischämiezeiten, Diagnose und Zustand des Empfängers sowie Technik und Umstände der Transplantation selbst. Die Bedeutung der einzelnen Faktoren wird unterschiedlich beurteilt und ist teilweise in erneute kritische Diskussion geraten (1), der resultierende Ischämieschaden beeinflußt jedenfalls die Ergebnisse erheblich, denn im Falle einer irreversiblen Nicht-Funktion, mit der in ca. 5 – 10% oder mehr gerechnet werden muß (2), besteht die einzige Chance in einer Retransplantation, die allerdings, bei INF, verglichen mit anderen Indikationen, die schlechteste langfristige Prognose hat (2) und auch nach eigenen Erfahrungen nur bei sehr frühzeitiger Indikationsstellung erfolgreich durchgeführt werden kann. Entscheidend für den Erfolg ist daher eine frühzeitige diagnostische Sicherheit hinsichtlich der Irreversibilität des Ischämieschadens.