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.

Only B lymphocytes induce active enhancement of rat cardiac allografts.

LEW rats were immunized 7 days before (LEW X BN)F1 heart transplantation with 10(7) BN donor cells, either purified erythrocytes (RBC), peripheral blood (PBL), splenic, nylon-wool-adherent (B-enriched) or nylon-wool-nonadherent (T-enriched) lymphocytes. Allograft rejection was only significantly enhanced in animals pretreated with lymphocyte populations containing surface immunoglobulin (SIgG)-positive cells (PBL, splenic, or B-enriched lymphocytes). Recipients immunized with RBC or T-enriched lymphocytes containing few, if any, SIgG-bearing B lymphocytes showed no significant graft prolongation.

Energy-dependent injury to cultured sinusoidal endothelial cells of the rat liver in UW solution.

The critical injury to liver during cold preservation is believed to occur to the sinusoidal endothelium. In this study the viability of cultured sinusoidal endothelial cells from rat liver was assessed during storage in University of Wisconsin solution at 4 degrees C. The vast majority of cells (83 +/- 12%) died within 24 hr of storage. Addition of KCN (1 mM) to the solution to simulate hypoxia markedly increased survival: only 3 +/- 2% of cells had lost viability after 24 hr in the presence of cyanide. Further experiments showed that other inhibitors of mitochondrial ATP formation (antimycin A 1 microM, rotenone 1 microM, oligomycin 10 microM, carbonyl cyanide m-chlorophenylhydrazone 1 microM) were protective as well, whereas glucose (10 mM) greatly diminished the protective effect of cyanide (loss of viability 38 +/- 7% after 24 hr). ATP measurements confirmed the correlation between the energy state of the cells and cell death: ATP levels after 6 hr of incubation were 19.9 +/- 4.0 nmol/10(6) cells in UW solution, 13.7 +/- 2.9 nmol/10(6) cells in UW + glucose, 6.9 +/- 1.9 nmol/10(6) cells in UW + KCN + glucose and 1.9 +/- 1.5 nmol/10(6) cells in UW + KCN. In contrast to the protective effect observed in UW solution, addition of KCN to Krebs-Henseleit buffer led to increased endothelial cell damage upon cold storage. We therefore conclude that in UW solution damage to the sinusoidal endothelium is energy-dependent.

Adenine nucleotide metabolism and its relation to organ viability in human liver transplantation.

The relationship between adenine nucleotide metabolism and ischemic damage was studied in human liver. Thirty transplanted grafts were divided into two groups according to their functional outcome. Cellular adenine nucleotide levels were assayed by high-performance liquid chromatography. During cold ischemia, the adenosine triphosphate (ATP) level was not correlated with graft function, but two grafts with low total adenine nucleotides (TAN) levels showed poor function after transplantation. After recirculation, the ATP level showed good recovery in grafts that functioned satisfactorily (n = 24, 5.47 +/- 1.51 mumol/g dry weight), but remained low in poorly functioning grafts (n = 6, 3.30 +/- 1.68 mumol/g dry weight) (P less than 0.01). The level of recovery of ATP was inversely related to the period of warm ischemia during implantation (P less than 0.01). Bile production, used as a parameter of initial function, was observed shortly after implantation in 17 of 24 grafts that functioned satisfactorily, but in only 1 of 6 poorly functioning grafts. It is concluded that loss of adenine nucleotides and lack of bile production during transplantation are good markers of damaged grafts in human liver transplantation.

The course of untreated acute rejection and effect of repeated anti-CD3 monoclonal antibody treatment in rhesus monkey liver transplantation.

The effect of single and repeated treatment of liver allograft rejection using an anti-CD3 monoclonal antibody (FN18) was studied in a rhesus monkey model. Eight RhLA-mismatched monkeys received initial postoperative immunosuppression with CsA/prednisolone for 28 days. After cessation, acute rejection occurred in all animals (days 28-50). Control animals (n = 3) receiving no rejection treatment developed a chronic progressive rejection and died at days 112-160. In the animals treated with FN18 (n = 5), the first acute rejection was successfully reversed. T lymphocytes were cleared from the peripheral blood and the graft. Increased class I and class II MHC-antigens on hepatocytes were reduced to normal levels within 5 days of treatment. The second rejection treatment remained ineffective in two animals with antiidiotypic antibodies to FN18 but was successful in two animals with a low antimouse response. These four animals survived 160-509 days. The results have a number of implications regarding the course of untreated rejection in human liver transplant recipients and repetitive rejection treatment with monoclonal antibodies.

Noninvasive procedures for diagnosis of renovascular hypertension in renal transplant recipients--a prospective analysis.

The purpose of this study was to clarify the selectivity and specificity of noninvasive procedures for diagnosis of clinically suspected posttransplant renovascular hypertension. We prospectively investigated 25 renal transplant recipients with arterial hypertension and clinically suspected stenosis of the graft artery (8 female and 17 male patients; ages 45 +/- 15 years). We performed a captopril test with 25 mg captopril (n = 25), renography with technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) before and after angiotensin-converting enzyme (ACE) inhibition with determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) (n = 23) and color-coded duplex ultrasonography of the transplant kidney vessels (n = 24). Renal transplant artery stenosis (RTAS) was excluded by renal arteriography in 20 patients and by operative evaluation or clinical follow-up in 5 patients. We identified 4 patients with RTAS and renovascular hypertension. The noninvasive methods showed the following results (sensitivity/specificity): (1) captopril test: 75%/67%; (2) renography combined with ACE-inhibition: 75%/84%; and (3) color-coded duplex ultrasonography: 100%/75%. We conclude that in patients with clinical evidence of RTAS most noninvasive diagnostic procedures are not sufficiently accurate to exclude the diagnosis. Only color-coded duplex ultrasonography did not fail to detect all patients with RTAS and may act as a screening test. Intraarterial renal angiography remains the most reliable and as-yet indispensable diagnostic test for transplant recipients to rule out RTAS.

Posttransplant renal artery stenosis--outpatient intraarterial DSA versus color aided duplex Doppler sonography.

A prospective trial was conducted to assess the accuracy of color aided duplex Doppler (CADD) sonography to rule out transplant renal artery stenosis (TRAS) and to determine feasibility and safety of intraarterial digital subtraction angiography (DSA) in hypertensive renal allograft recipients on an outpatient basis. All patients were hypertensive (n = 18, mean age: 42 +/- 11 years) and underwent CADD and an i.a. DSA with 4F catheters. There was a 4 hour rest post DSA. Duplex Doppler measurements of maximum velocity were obtained. Absolute values of > or = 100 cm/s were considered indicative to suspect TRAS. DSA revealed severe TRAS in 4 patients (22%). The stenoses were located near the iliorenal anastomosis (n = 2) and at the bifurcation of the renal artery (n = 2). Duplex Doppler classified twelve (67%) renal artery pedicles normal (maximum velocity: 79 +/- 23 cm/s). TRAS was suspected in 6 patients with a maximum velocity of 159 +/- 48 cm/s (P < 0.01). False positive CADD diagnoses were due to tortuous graft vessels and a postbiopsy arteriovenous fistula. Sensitivity of CADD was 100%, specificity 86%. There were no DSA related complications. No impairment of graft function occurred. CADD allows renal angiography to be reserved to clarify an inconclusive ultrasound study and for definite diagnosis of angiomorphology and lesion classification. Intraarterial DSA of renal grafts in outpatients may be performed without an increased risk of procedure-related complications.

[Chemoembolization of primary liver cancer using epirubicin-lipiodol]. / Chemoembolisation primärer Leberkarzinome mit Epirubicin-Lipiodol.

The double supply of the liver allows one to perform specific embolisation of liver carcinomas since these are mostly supplied arterially. According to their occlusion characteristics--central, peripheral, capillary--different embolising materials are suitable for tumour embolisation under varying conditions. Oily substances cause capillary occlusion and can be used in conjunction with chemotherapeutic agents. This study deals with the results from lipiodol-epirubicin embolisation in 25 patients with hepatocarcinomas and cholangiocarcinomas. In a three-and-a-half year follow-up period 16 of these 25 patients died, maximum survival time being 28.4 months. Survival varied from 9.2 to 28.4 months compared with a survival time of 2-8 months in untreated patients. In this case hypervascular tumours have a better prognosis than the rarer hypovascular tumours because of improved deposition and activity of the chemotherapeutic agent.

[The chemoembolization of hepatocellular carcinoma: the computed tomographic findings and clinical results in prospective repetitive therapy]. / Chemoembolisation des hepatozellulären Karzinoms: computertomographische Befunde und klinische Resultate bei prospektiv repetitiver Therapie.

Between April 1989 and March 1993 162 transarterial chemoembolizations (TACE) were performed repeatedly (mean interval: 2.9 months) in 52 patients with hepatocellular carcinoma (HCC): An emulsion of Lipiodol and epirubicin was injected as selectively as possible in a dosage proportional to liver function and tumour size. Before and after each TACE the size of tumours and ratio of tumour volume containing Lipiodol (RTVCL) were determined in CT and the grade of tumour vascularisation was assessed angiographically. The RTVCL increased from 58% after the first treatment to 73% after the third treatment. RTVCL and Lipiodol retention were higher in responders than in non-responders. Tumours with expansive growth pattern showed a higher response rate (56%) than infiltrating tumours (20%). Mean survival of these patients was different (19 and 8 months; p < 0.01), respectively. Survival rates of all patients were 54, 22, and 11% after 1, 2 and 3 years, respectively. Repeated TACE shows local effectiveness. Three treatments during a period of one year are recommended for patients with Child-Pugh class A cirrhosis.

[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.

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.

[Liver transplantation in childhood]. / Lebertransplantation im Kindesalter.

From 1977 to 1985 altogether 143 children were referred to our hospital for liver transplantation. These children were aged 6 months to 15 years. According to the results of a defined examination protocol liver transplantation was indicated in 102 of these children. Contraindications were observed in 17 patients. In 14 children liver transplantation was not yet indicated. Parents of 8 children refused transplantation. Only 30 children have been transplanted so far. Out of these, 21 actually survive. The cumulative 5-year survival rate after transplantation is calculated to be 60.5%.

[Reflux-preventing gastric resection. An animal experiment study]. / Refluxverhütende Magenresektion. Eine tierexperimentelle Studie.

In 30 pigs the prevention of duodenogastric reflux following distal gastrectomy through different types of jejunal transposition or Roux-en-Y-gastroenterostomy was studied. The reflux was measured by determination of the intragastric amounts of bile acids and lysolecithin, and by the total number of glycerophosphatids. After distal gastrectomy and proximal selective vagotomy, isoperistaltic jejunal segments of different lengths were transposed between gastric remnant and duodenum. The reflux was normalized by 25-cm segments. Shorter segments led to no significant decrease of the reflux. The jejunal invagination of additional isoperistaltic valve did not have a significant effect. The same protection as from 25-cm segments was obtained by Roux-en-Y-gastrojejunostomy. The role of the duodenogastric reflux following gastrectomy for the gastric mucosa is disucssed. The necessity of the reparation of the pyloric function is shown.

[Treatment of symptomatic non-parasitic liver cysts using percutaneous drainage and irrigation with hypertonic saline solution]. / Behandlung der symptomatischen nichtparasitären Lebercysten mittels percutaner Drainage und Spülung mit hypertoner Kochsalzlösung.

In 7 patients with a total of 20 symptomatic larger liver cysts an instillation therapy with 20% saline solution was performed via a sonographically placed sump drainage. No clinically relevant complications were observed. After a median follow-up period of 18 months in two patients with cystic livers asymptomatic residual cysts measuring less than 4 cm were found only. In comparison to the instillation therapy using a sclerosing agent the presented technique seems to be equally effective but less traumatizing. Surgical procedures are restricted to a few, otherwise not treatable patients.

Prevention of reflux after gastro resection in the pig.

In 48 pigs the duodenogastric reflux of bile acids and lysolecithin is studied after different types of gastroduodenostomy, jejunal interposition and Roux-Y-gastroenterostomy. The intragastric concentrations of bile acids and lysolecithin were found to be pathologically elevated after gastroduodenostomy. There was no difference between end-to-end, end-to-side or supraduodenal end-to-side anastomoses. An effective reflux prevention was possible by interposition of 25 cm of isoperistaltic jejunum or by Roux-Y. A shorter (15 cm) interposition with or without an isoperistaltic invagination valve was not sufficient in normalizing reflux amounts.

[The status of liver transplantation 1992]. / Stand der Lebertransplantation 1992.

Transplantation of the liver has progressed in recent years and has become universally accepted for numerous indications of end-stage liver diseases, predominantly cirrhosis induced by viral hepatitis (HBV/HCV), acute hepatic failure and primary biliary cirrhosis. Interdisciplinary research is devoted to prevention of recurrent disease: Risk groups have been defined, in which HBV recurrence can be prevented by immunoprophylaxis. The risk of tumor recurrence can be calculated, adjuvant chemotherapy might improve prognosis of patients with small incidental tumors.

[Acute liver failure: current hepatological-surgical therapy results]. / Akutes Leberversagen: aktuelle hepatologisch-chirurgische Therapieverfahren.

For fulminant hepatic failure the prognosis is depending on the onset of severe encephalopathy (coma grade III to IV), cerebral oedema, renal and respiratory failure. Treatment strategies must be devoted to limit these complications and proceed with an urgent liver transplantation. Overall 1-year survival rates after hepatic transplantation in fulminant liver failure are as high as 80%.

[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.