Detection of potential organ donors: 2-year analysis of deaths at a German university hospital.

OBJECTIVE: In 2006, inhouse coordinators were introduced in all hospitals with intensive care units in Baden-Württemberg to improve organ donation. At our university hospital with a neurosurgery and a transplantation unit, we analyzed whether brain death certification and donation requests were always initiated (if possible). MATERIALS AND METHODS: We retrospectively reviewed all 1312 hospital deaths from 2006-2007 by studying medical records and consulting with physicians. The possibility of organ donation was questioned. RESULTS: Donation was requested among 68/702 deaths due to cerebral complications. A request was impossible in 8 cases. Consent for donation was obtained in 29 cases, and it was realized in 24 cases. In 14 cases of resuscitation from shock or cardiac failure, therapy was not continued because of questionable hemodynamic stability. In 17 cases admitted to peripheral wards and 19 to intensive care units death due to cerebral complications occurred within 48 hours, but medical records were not relevant for exclusion criteria for organ donation. CONCLUSIONS: The detection of donors was not acceptable. In patients without a prognosis after resuscitation, further hemodynamic stabilization was frequently omitted, because organ donation had not been considered. In cases of donation requests the refusal rate was high. We initiated specific training.

Expanded criteria liver donors (ECD): effect of cumulative risks.

UNLABELLED: The use of ECD in liver donors increases the risk of primary non function (PNF). The German Medical Association (2004) defined an ECD, if one of the following conditions existed: high risk of disease transmission, hemodynamic deterioration, donor age > 65years, BMI > 30kg/m2, bilirubine > 51 mmol/l, ASAT or ALAT > 3*reference, sodium > 165 mmol/l, days on ICU > 7, steatosis > 40% or equivalent liver pathologies. The effect of ECD-criteria was assessed. METHODS: Out 422 consecutive donors (1992-2004) with 282 liver grafts were transplanted (LTX) the existing ECD criteria were cumulated per donor (sigmaECD), grouped and compared to the number of grafts used and the one year graft function rate (all grafts/censored for grafts lost due to PNF only). Discrimination was determined by Receiver-Operating-Characteristics (ROC). RESULTS: With increasing sigmaECD the rate of grafts procured declined (sigmaECD = 0: 95% [n = 162], sigmaECD = 1: 62% [n = 146], EECD = 2: 39% [n = 61], sigmaECD = 3: 32% [n = 38], sigmaECD > or = 4: 13% [n = 16], p < 0.0001). Similarly the one year graft function rate diminished (all grafts: sigmaECD = 0: 72%, sigmaECD = 1: 70%, sigmaECD = 2: 75%, sigmaECD = 3: 58%, sigmaECD > or = 4: 0%, p = 0.0801; censored for grafts lost due to PNF: sigmaECD = 0: 99%, sigmaECD = 1: 95%, sigmaECD = 2: 100%, sigmaECD= 3: 67%, sigmaECD > or = 4: 50%, p < 0.0001). The best cut off for prediction of grafts used was a sigmaECD of 0-1 vs. 2-5 (sensitivity 55%, specificity 87%). The one year graft function rate was adversely affected in sigmaECD above 3. All three grafts used for LTX with confirmed severe steatosis at donor operation (n = 3) did not function. CONCLUSION: Grafts from ECD can be used for LTX. Cumulated ECD was associated with an increased risk of PNF requiring retransplantation. Despite this fact not using donors with cumulated ECD will decrease the limited donor pool. Such livers should be ideally allocated regionally to avoid additional ischemic-reperfusion damage.

[Chemoembolization of hepatocellular carcinomas: which factors determine therapeutic response and survival?]. / Chemoembolisation des hepatozellulären Karzinoms: Welche Faktoren bestimmen Therapieansprechen und Uberleben?

PURPOSE: To determine independent prognostic factors influencing the survival of patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Ninety-one patients with unresectable HCC were treated with 269 repetitive TACE. The dosages of epirubicin (40-60 mg) and ethiodized oil (8-20 ml) were adjusted to tumor size and liver function. The impact of tumor size, macroscopic tumor type, tumor location, portal vein infiltration, capsular infiltration, tumor vascularization, uptake of ethiodized oil within the tumors, Child-Pugh-Class and Okuda-Stage on patient survival were evaluated by means of univariate and multivariate regression analysis. RESULTS: The following independent prognostic factors were found: tumor type (nodular vs. infiltrating, p = 0 008), tumor size (p = 0.01), Child-Pugh-Class (A vs. B; p = 0.02) and grade of tumor vascularization (p = 0.04). In 57 patients with HCC of the nodular type, the median survival time was significant longer than in 32 patients with HCC of the infiltrating type (17.0 months vs. 7.9 months; p < 0.003; 2 tumors could not be classified). The 1-, 2- and 3-year-survival rates were significantly higher in 57 patients with Okuda-Stage I disease, compared to 34 patients with Okuda-Stage II and III disease (73%, 31% and 8% vs. 23%, 6% and 4% p < 0.0001). CONCLUSIONS: Tumor type, tumor size and grade of liver cirrhosis have an independent impact on prognosis of patients with HCC treated by TACE. An appropriate selection of patients is necessary to improve patients survival.

Endotoxemia in organ donors: graft function following liver transplantation.

Translocation of endotoxin (LPS) to the portal-venous system is produced by multiple factors. In the case of normal liver function, LPS is rapidly cleared from the portal blood by Kupffer cells; in impaired liver function, LPS can reach the systemic circulation. The objective of this study was to investigate whether elevated donor endotoxin levels affect graft function in the recipient. LPS levels in donor plasma were measured in 14 consecutive liver transplantations. Grafts with donor LPS levels < or = 12 pg/ml had a function probability of 100% after 600 days (n = 10). LPS concentrations of > 12 pg/ml in donor plasma led to loss of function in 75% of the liver grafts (n = 4; P = 0.003; Wilcoxon). Elevated LPS values in donor plasma seem to impair the prognosis of the grafts and could predict poor graft function as early as at the time of brain death.

The quality of a liver graft.

Because transplantation success is influenced by the quality of the graft, the objective of this study was to find parameters to evaluate transplant livers in the recipient centre. In 64 liver grafts, the venous effluates of a portal back-table flush were investigated for various parameters. Amongst them, glutathione S-transferase (GST), glutamate dehydrogenase (GLDH) and the leucocyte count were found superior in predicting graft survival. Using the combination of these parameters, 100-day graft survival of between 95% (all parameters positive) and 0% (all parameters negative) was predicted. We concluded that good liver grafts are characterized by a low width of injury (cytosolic component: GST), a low depth of injury (mitochondrial component: GLDH), as well as by a potential to induce tolerance (passenger leucocytes). Perfusate analysis seems to be a valuable tool to recognize problematic grafts in advance and to quantify the "graft factor" in considerations concerning quality control.

Influence of perioperative sHLA I concentrations on the histological development of the liver graft.

Soluble HLA I (sHLA I) in human serum are ascribed an immunoregulatory role in the context of organ transplantation. Based on histological findings, the objective of the current study was to evaluate the protective influence of sHLA I in liver transplantation from the time point of reperfusion. The sHLA I concentrations in serum samples derived from the liver vein immediately after reperfusion (flush catheter) of 38 patients with liver transplantations were determined by ELISA. The postoperative histological findings of the transplant biopsies were categorized according to rejection, endothelialitis, cholestasis, and necrosis, as well as fatty degeneration. An evaluation according to Kaplan-Meier showed a lower incidence for all of these factors in liver grafts with high sHLA concentrations (P < 0.05). We conclude that low sHLA I concentrations during reperfusion correlate with later complications, thus indicating that sHLA I may have protective potential in liver transplantation.

MR imaging and (1)H spectroscopy of brain metabolites in hepatic encephalopathy: time-course of renormalization after liver transplantation.

PURPOSE: To evaluate changes in hydrogen 1 magnetic resonance (MR) spectroscopic findings in overt or subclinical hepatic encephalopathy (HE) after liver transplantation and to compare these changes with clinical outcomes and basal ganglia high signal intensity (BGH). MATERIALS AND METHODS: Twenty-two patients scheduled for liver transplantation and 17 healthy control subjects were examined with (1)H MR spectroscopy and standard nonenhanced MR imaging. Eight patients underwent complete MR imaging and (1)H spectroscopic examinations before liver transplantation and at 3-4-week, 12-28-week, and 10-12-month follow-up after liver transplantation. RESULTS: Before liver transplantation, typical (1)H spectroscopic changes-decreased myo-inositol (mI)/creatine (Cr) and choline (Cho)/Cr ratios and an elevated glutamine and glutamate (Glx)/Cr ratio-were found in 21 patients. Eighteen patients had BGH at T1-weighted imaging. Three to 7 months after liver transplantation, the mI/Cr and Glx/Cr ratios were within the normal range in five of eight and eight of eight patients, respectively, without any residual signs of subclinical or overt HE; however, at MR imaging, seven patients still had BGH. CONCLUSION: After successful liver transplantation, renormalization of HE-specific brain metabolite changes is detected at (1)H spectroscopy and precedes the disappearance of BGH. The neuropsychologic signs of subclinical or overt HE follow the changes seen at (1)H spectroscopy rather than those seen at MR imaging.

Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.

In hepatorenal syndrome (HRS), renal insufficiency is often progressive, and the prognosis is extremely poor under standard medical therapy. The molecular adsorbent recirculating system (MARS) is a modified dialysis method using an albumin-containing dialysate that is recirculated and perfused online through charcoal and anion-exchanger columns. MARS enables the selective removal of albumin-bound substances. A prospective controlled trial was performed to determine the effect of MARS treatment on 30-day survival in patients with type I HRS at high risk (bilirubin level, > or =15 mg/dL) compared with standard treatment. Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999. All were Child's class C, with Child-Turcotte-Pugh scores of 12.4 +/- 1. 0, United Network for Organ Sharing status 2A, and total bilirubin values of 25.7 +/- 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration (HDF) and standard medical therapy, and 5 patients were in the control group (HDF and standard medical treatment alone). None of these patients underwent liver transplantation or received a transjugular intrahepatic portosystemic shunt or vasopressin analogues during the observation period. In the MARS group, 5.2 +/- 3.6 treatments (range, 1 to 10 treatments) were performed for 6 to 8 hours daily per patient. A significant decrease in bilirubin and creatinine levels (P <.01) and increase in serum sodium level and prothrombin activity (P <.01) were observed in the MARS group. Mortality rates were 100% in the control group at day 7 and 62.5% in the MARS group at day 7 and 75% at day 30, respectively (P <.01). We conclude that the removal of albumin-bound substances with the MARS method can contribute to the treatment of type I HRS.

Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support.

The use of xenogenic or genetically engineered cell types in bioartificial liver support systems requires separation methods between the patients' blood and the liver support bioreactors that guarantee the sufficient transfer of pathophysiologically relevant substances but prevent complications. The present paper describes a new membrane separation system that is nearly impermeable to proteins but enables the exchange of water soluble and protein bound toxins by a special membrane and a recycled protein containing dialysate. Because the full range of toxins in hepatic failure has still not been identified, the value of this membrane separation method was evaluated clinically. Thirteen patients suffering from life threatening hepatic failure who had not responded to state of the art therapy were treated with this device, the molecular adsorbent recycling system (MARS). The overall survival rate was 69%. All patients showed positive response to the therapy, indicating that the presented membrane separator combines therapeutic effectivity with the highest safety criteria for the patient by cutting the exchange of substances below the level of proteins.

Introducing fluorine-18 fluoromisonidazole positron emission tomography for the localisation and quantification of pig liver hypoxia.

Fluorine-18 labelled fluoromisonidazole ([18F]FMISO) has been shown to accumulate in hypoxic tissue in inverse proportion to tissue oxygenation. In order to evaluate the potential of [18F]FMISO as a possible positron emission tomography (PET) tracer for imaging of liver tissue hypoxia, we measured the [18F]FMISO uptake in 13 domestic pigs using dynamic PET scanning. Hypoxia was induced by segmental arterial hepatic occlusion. During the experimental procedure the fractional concentration of inspired oxygen (FiO2) was set to 0.67 in group A (n=6) and to 0.21 in group B (n=7) animals. Before and after arterial occlusion, the partial pressure of O2 in tissue (TPO2) and the arterial blood flow were determined in normal flow and flow-impaired liver segments. Standardised uptake values [SUV=kBq tissue (in g) / body weight (in kg) x injected dose (in kBq)] for [18F]FMISO were calculated from PET images obtained 3 hours after injection of about 10 MBq/kg body weight [18F]FMISO. Immediately before PET scanning, the mean arterial blood flow was significantly decreased in arterially occluded segments [group A: 0. 41 (0.32-0.52); group B: 0.24 (0.16-0.33) ml min-1 g-1] compared with normal flow segments [group A: 1.05 (0.76-1.46); group B: 1.14 (0.83-1.57) ml min-1 g-1; geometric mean (95% confidence limits); P<0.001 for both groups]. After PET scanning, the TPO2 of occluded segments (group A: 5.1 (4.1-6.4); group B: 3.5 (2.6-4.9) mmHg] was significantly decreased compared with normal flow segments [group A: 26.4 (21.2-33.0); group B: 18.2 (13.3-25.1) mmHg; P<0.001 for both groups]. During the 3-h PET scan, the mean [18F]FMISO SUV determined in occluded segments increased significantly to 3.84 (3.12-4.72) in group A and 5.7 (4.71-6.9) in group B, while the SUV remained unchanged in corresponding normal liver tissue [group A: 1.4 (1.14-1. 71); group B: 1.31 (1.09-1.57); P<0.001 for both groups]. Regardless of ventilation conditions, a significant inverse exponential relationship was found between the TPO2 and the [18F]FMISO SUV (r2=0. 88, P<0.001). Our results suggest that because tracer delivery to hypoxic tissues was maintained by the portal circulation, the [18F]FMISO accumulation in the liver was found to be directly related to the severity of tissue hypoxia. Thus, [18F]FMISO PET allows in vivo quantification of pig liver hypoxia using simple SUV analysis as long as tracer delivery is not critically reduced.

Diagnosis and management of metastatic gastrinoma by multimodality treatment including liver transplantation: report of a case.

Neuroendocrine tumors of the pancreas are being recognized with increasing frequency, not because the incidence has increased, but as a result of improvements in diagnostic tools such as radioimmunoassays for a variety of circulating peptides, and imaging methods that include positron emission tomography (PET) and immunoscintigraphy. Nevertheless, establishing the diagnosis of a neuroendocrine tumor is always a challenge to the clinician from both diagnostic and therapeutic perspectives. Liver transplantation as the ultimate therapeutic, or at least palliative, option for hepatic metastases has produced contradictory results over the past decade. We report herein the case of a 23-year-old woman who, after being diagnosed with gastrinoma in 1989, underwent the complete therapeutic array including liver transplantation for hepatic metastases in 1991. Although an extrahepatic tumor recurred 2 years later, for which double chemotherapy with 5-FU and streptozotocin was given, she is currently leading a normal life with a full-time job. This case prompted a critical review of the current literature on diagnosis and medical and surgical treatment.

The radiological management of biliary complications following liver transplantation.

PURPOSE: Biliary complications contribute significantly to morbidity and mortality in the liver transplant recipient. Surgery has been the mainstay of therapy, but interventional radiological techniques have made significant progress. METHODS: Diagnostic percutaneous transhepatic cholangiography (PTC) was performed in 12 patients; percutaneous transhepatic drainage (PTD) was performed in 10 patients. Additional interventional procedures included laser lithotripsy, biopsy, dilatation, and stent implantation. RESULTS: In 6 patients PTC revealed anastomotic, and in 6 patients nonanastomotic biliary strictures. Four patients had intrahepatic stones. Biliary strictures were treated by implantation of Palmaz stents in 5 of 6 patients with anastomotic strictures, and in 3 of 6 patients with nonanastomotic strictures. The intrahepatic stones were fragmented with dye laser lithotripsy under cholangioscopic control in 3 of 4 patients. One spontaneous stent migration after 24 months and one stent occlusion were observed; the remaining stents are still patent. Patients with anastomotic strictures had a more favorable outcome: 5 of 6 of these patients are still alive and symptom-free after an average of 27.4 months, but only 3 of 6 patients with nonanastomotic strictures are alive after an average of 9.8 months. CONCLUSION: The different outcomes in patients with anastomotic versus nonanastomotic strictures may be explained by the different causes of these types of stricture.

[Does piggy-back liver transplantation have a detrimental effect on venous drainage?--A comparative duplex ultrasound study]. / Hat die Piggy-back Lebertransplantation einen nachteiligen Einfluss auf den venösen Abfluss?--Eine duplexsonographische Vergleichsstudie.

Venous drainage in "Piggy-back" Liver Transplantation "Piggy-back" orthotopic liver transplant (OLT) may offer some advantages (hemodynamic stability without veno-venous bypass) over standard OLT, but there is concern about the risk of venous outflow obstruction associated with this technique. In this study (n = 19 piggy-back, n = 12 standard OLT) it was possible to show, by means of duplex scanning, that flow velocity, resistance and flow of hepatic veins do not differ significantly.

[Liver transplantation 1994]. / Lebertransplantation 1994.

Transplantation of the liver has progressed in recent years and has become universally accepted for numerous indications in end-stage liver diseases, predominantly primary biliary cirrhosis, sclerosing cholangitis, biliary atresia and liver-related metabolic disorders. In fulminant and subfulminant hepatitis, prognosis has been improved considerably by liver transplantation. The debate still persists whether liver transplantation might be indicated in diseases recurring after transplantation, such as HBV cirrhosis. Alcoholic cirrhosis as an indication for transplantation remains still controversial. The risk of tumor recurrence after transplantation for small hepatocellular carcinoma in cirrhosis can be calculated; adjuvant chemotherapy might increase prognosis. Transplantation for other malignant liver tumors seems to be obsolete.

The potential role of reactive oxygen species in liver ischemia/reperfusion injury following liver surgery.

Reperfusion of a previously ischemic tissue may lead to an aggravation of injury. The liver has been shown to be susceptible to this reperfusion injury in several experimental systems. Reactive oxygen species appear to play an important role in the development of such injury, as has been demonstrated by direct measurements of their release, and by the protective effects of antioxidants. Upon reperfusion, reactive oxygen species may be released by hepatocytes, Kupffer cells and neutrophils. The relative contribution of the various liver cell types to the release of reactive oxygen species depends on several factors, including the duration and condition of ischemia and the time elapsed after reperfusion. There is only limited evidence for the occurrence of reperfusion injury in humans following liver surgery. The role of reactive oxygen species in this injury in humans remains to be shown.