[Disposition for organ donation: analysis of a survey and trial of 974 respondents]. / Organspendebereitschaft: Interventionsstudie bei 974 Befragten.

BACKGROUND: Due to the lack of donor organs many patients cannot be helped in time with the necessary transplantation in Germany. At the same time, there is an organ donor potential that is not being exploited. A high refusal rate with a low rate of organ donor card holders remains problematic. The objective of this study was to collect the rate of holders of organ donor cards in a collective and to evaluate the collective according to other attributes in the context of a targeted trial. METHODS: In 2009, a three-part questionnaire including an educational text regarding the topic of "organ donation" was sent out to the employees of the Sparkasse Essen (a savings bank). RESULTS: Altogether, 974 out of 1480 (65.8 %) completely answered questionnaires were evaluated. 21.3 % of the respondents had an organ donor card at the time the survey was carried out. A statistically significant association between gender (p value, 0.0438), age (p value, 0.0267) and the possession of a donor card could be determined. 22.1 % of the respondents who participated in sports regularly or donated blood (p value, < 0.0049), were holding an organ donor card. 60 % of the respondents found the brief information to be sufficient, 22.6 % could imagine acquiring an organ donor card for them based on the presented information alone. CONCLUSION: The spread of information and transparency in transplant medicine are essential for the facilitation of "willingness to donate organs". In the framework of this trial, besides data analysis, also fundamental information on "organ donation" could be conveyed. After all, 95.3 % of the respondents have read the information material and hence document the success of the study.

Neuromonitoring in a porcine model of acute hepatic failure.

Cerebral oedema has been noted to occur frequently in patients dying of fulminant hepatic failure. Therefore, in the present study, multimodal neuromonitoring was evaluated in an animal model of hepatectomy. Acute liver failure was surgically induced in swine by complete hepatectomy (n = 8). Intracranial pressure monitoring via a ventricular drainage system, electroencephalogram and recording of visually evoked potentials were used to establish a continuous neuromonitoring system. Measurements of liquor and serum ammonia (NH(3)) levels were taken at later stages of the trial in an approach to widen monitoring. Serial monitoring of the electroencephalogram revealed progressive slowing of the frequency with decreasing amplitude. Monitoring of the intracranial pressure with a subdural pressure transducer demonstrated a progressive and reproducible elevation. Increase in blood NH(3) was observed. Anaesthesia was terminal. In all cases death was caused by cardiocirculatory insufficiency, confirmed by autopsy. At autopsy, brain tissue of the animals was found to be swollen showing flattened cortical gyri. In conclusion, the technique of extended neuromonitoring offers an advanced option for monitoring animal models of fulminant hepatic failure for further developments and investigations.

Attitude of health care professionals to organ donation: two surveys among the staff of a German university hospital.

The persistent shortage of organs for transplantation could be minimized by increasing the number of potential donors. The opinion of the staff of a university hospital toward organ donation is of special interest because they are directly involved in solid organ transplantation. In 2007, we conducted a first voluntary survey concerning organ donation among the staff of the university hospital of Essen. A short information campaign and further opinion poll among staff as well as visitors was performed in 2009 to compare professional and public attitudes toward organ donation. The first poll comprised 242 questionnaires showing 55% of the hospital staff carrying organ donor cards, particularly more women (60%) than men (46%). After this survey, an additional 19% of the hospital staff imagined they might carrying an organ donor card in the future. In the second survey, we analyzed 151 questionnaires, showing 66% of staff members carrying an organ donor card, an incidence significantly greater than among visitors (48%). The need for information regarding organ donation was greater among visitors (35%). However, 21% of the hospital staff still also need education concerning organ donation. More education and increased transparency of transplantation practice are necessary for hospital staff to act successfully as initiators. Hospital staff with positive attitudes toward organ donation may have a positive impact on the attitudes of the general public toward organ donation.

[Kidney procurement and transplantation from a surgical perspective]. / Organentnahme und Nierentransplantation aus Sicht des Chirurgen.

Kidney transplantation is the best therapeutic option in many patients with end-stage renal disease, because it significantly increases lifespan over that of patients who remain on dialysis. Because of organ shortage the average waiting time for a suitable kidney in Germany is about four years after the onset of dialysis treatment. Currently about 80% of all transplanted kidneys are obtained from brain-dead patients. The possibility for kidney transplantation after living donation reduces the minimum waiting time to a few weeks. An optimized organizational strategy as well as donor and recipient preparation are possible in living donation, resulting in excellent transplant quality and a short cold-ischemia time. Pre-emptive kidney transplantation after living donation is an attractive treatment option without the need for previous dialysis and is also an option for children. The excellent long-term results after kidney transplantation have been caused by improvement of operative technique, organizational strategy, donor preparation, postoperative care and, in particular, immunosuppression.

Biotransformation of cyclosporin in primary rat, porcine and human liver cell co-cultures.

The purpose of this study was to investigate the species-specific cyclosporin biotransformation in primary rat, human, and porcine liver cell cultures, and to investigate the suitability of a modified sandwich culture technique with non-purified liver cell co-cultures for drug metabolism studies. A sandwich culture was found to enhance hepatocellular metabolic activity and improve cellular morphology and ultrastructure. The cyclosporin metabolites AM9 and AM1 were formed in porcine and human liver cell sandwich co-cultures at levels corresponding to the respective in vivo situations. In contrast, metabolite profiles in rat hepatocytes were at variance with the in vivo situation. However, for all cell types, the overall metabolic activity was positively influenced by sandwich co-culture. The initial levels of albumin synthesis were higher in sandwich cultures than in those without matrix overlay. It is hypothesized that the sandwich culture system provides an improved microenvironment and is, therefore, an advantageous tool for in vitro studies of drug metabolism.

Effects of positive end-expiratory pressure on systemic haemodynamics, with special interest to central venous and common iliac venous pressure in liver transplanted patients.

BACKGROUND AND OBJECTIVES: Positive end-expiratory pressure may alter cardiac function and systemic haemodynamics. As transplanted livers may be sensitive to liver congestion, the aim of our study was to evaluate the effect of positive end-expiratory pressure on the cardiovascular system and in particular on central venous and iliac venous pressure in liver transplanted patients. PATIENTS AND METHODS: Seventy-two liver transplant patients were enrolled in this prospective, interventional study. On admission to our Intensive Care Unit all patients were ventilated in a biphasic positive airway pressure mode. Haemodynamic effects of three randomly set levels of end-expiratory pressures (0, 5 and 10 mbar) were studied in the immediate postoperative period in all patients. Mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, central iliac venous pressure and cardiac index were recorded and analysed at each of the three end-expiratory pressure levels. RESULTS: The values of central- and wedge-pressure significantly increased with increased end-expiratory pressure. Central venous pressure increased by 24% and wedge pressure showed a 6% increase at 10 mbar in comparison to 0 mbar. The values for cardiac index and mean arterial pressure showed no statistically significant difference at 10 mbar as compared to 0 and 5 mbar. The mean pulmonary arterial and common iliac venous pressure were unaffected by different positive end-expiratory pressure levels. CONCLUSIONS: Short-term pressure controlled ventilation with end-expiratory pressure up to 10 mbar does not significantly impair systemic haemodynamics in liver-transplanted patients. Further studies are needed to determine whether these findings could be confirmed with higher pressure levels and/or over a longer period of ventilation time.

[Surgical therapy of intrahepatic cholangiocellular carcinoma]. / Chirurgische Therapie des intrahepatischen cholangiozellulären Karzinoms.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy. Tumor resection is the treatment of choice, but so far the value of hepatic resection has not been well defined. We report results with an aggressive surgical approach for the treatment of this tumor entity. PATIENTS AND METHODS: Between April 1998 and June 2004, 54 liver resections were performed in 120 patients with ICC. In 24 patients, 39 additional procedures were performed: resection of hilar bifurcation (n=18), partial resection of diaphragm (n=6), vascular resection and reconstruction (n=15). RESULTS: There were 30 R0, 21 R1, and three R2 resections. After R1/R2 resection and explorative laparotomy, the median survival times are 9 months and 6 months, respectively. Following R0 resection, the calculated median survival is 46 months, and the 1-, 3-, and 5-year survival rates are 83%, 58%, and 48%, respectively. CONCLUSION: The presented data show that R0 resection leads to a significant prolongation of survival in patients with ICC. In contrast, incomplete tumor removal does not provide a survival benefit. These results justify an aggressive surgical approach to achieve a R0 resection. The low resectability rate of less than 50% underlines the need for improved preoperative staging.

Biliodigestive anastomosis after intraoperative irradiation in swine.

A large animal model was established to investigate the feasibility and suitable dosage of intraoperative radiation therapy (IORT) to the hepatic hilum before biliary-enteric anastomosis is performed. Twenty-two Pietrain Hampshire pigs underwent gallbladder and proximal bile duct resection followed by IORT using 20-40 Gy and performing biliary-enteric anastomosis. In the follow-up period of 56 days, pigs developed dose-dependent complications like stenosis of the biliary-enteric anastomosis. Results demonstrate that IORT of the liver hilum up to 20 Gy is safe with acceptable early complications in the presented animal model. The porcine biliary-enteric anastomosis can tolerate intraoperative irradiation up to a dosage of 40 Gy without disruption.

New surgical technique for portal venous port system in Swine.

The need for serial blood sampling and continuous infusion using the portal vein for experimental surgery and pharmacological studies is evident. As suitable animal models are rare, we established a new technique to implant a permanent vascular access device to the portal vein in swine. All operations in study animals (n=8) were technically feasible due to a regularly detected side branch of the portal vein within the inferior pancreatic region; complications did not occur. Mean operation time was 48+/-17 min. This study clearly shows that the portal venous access is feasible and can be achieved safely using the inferior pancreatic vein for a permanent vascular access port system.

Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis.

BACKGROUND: Hepatocellular carcinoma (HCC) arising in normal liver parenchyma is rare and the outcome after hepatectomy is not well documented. METHODS: Between June 1998 and September 2003, 33 patients without viral hepatitis underwent resection for HCC in a non-cirrhotic, non-fibrotic liver. Data were analysed with regard to operative details, pathological findings including completeness of resection, and outcome as measured by tumour recurrence and survival. RESULTS: Twenty-three major hepatectomies and ten segmentectomies or bisegmentectomies were performed. After potentially curative resection, 19 of 29 patients were alive at a median follow-up of 25 months, with calculated 1- and 3-year survival rates of 87 and 50 per cent respectively. Survival was significantly better after resection of tumours without vascular invasion (3-year survival rate 89 versus 18 per cent; P = 0.024). Disseminated recurrence developed in nine of 29 patients, leading to death within 28 months of operation in all but one of the nine. CONCLUSION: These data justify hepatic resection for HCC arising in non-cirrhotic, non-fibrotic liver without underlying viral hepatitis. Liver transplantation is rarely indicated because the outcome is good after resection of tumours without vascular infiltration, whereas vascular invasion is invariably associated with diffuse extrahepatic recurrence.

[Organ transplantation in human immunodeficiency virus-infected patients. Results of a survey in German transplantation centres]. / Vollorgantransplantation bei Patienten mit HIV-Infektion. Ergebnisse einer Umfrage an deutschen Transplantationszentren.

BACKGROUND: Despite considerable advances following the introduction of highly active antiretroviral therapy, organ transplantation is usually denied categorically for human immunodeficiency virus (HIV) patients, and it is presented in German transplantation law as a contraindication. Today, this should be questioned critically. METHOD: A survey at all 87 German transplant centres was done concerning (1) how many HIV-positive patients were transplanted before and after February 2000, (2) willingness of the centres to transplant HIV-infected patients in the future, and (3) course of transplanted HIV patients so far. RESULTS: With a response rate of 78%, 39% of the questioned centres were accepting HIV patients in the future for transplantation, and 39% rejected this. Twenty percent voted for individual case decision. Three centres had practiced liver transplantation in 11 patients. CONCLUSION: The decision to transplant HIV-positive patients in Germany is mostly based on individual cases and not refused in general. However, prospective studies on this issue are justified and needed.

[Liver transplantation in elderly patients]. / Lebertransplantation bei älteren Patienten.

Since the first liver transplantation (OLT) was performed by Starzl in 1963, this has become the standard therapy for end stage chronic liver disease and acute hepatic failure. It is also the therapy of choice in selected cases of hepatic malignancy. Due to the optimization of intra- and perioperative management, new immunosuppressant drugs and improved organ procurement, the clinical outcome in patient and graft survival has increased continuously. The shortage of donor organs has led to the development of new surgical techniques such as split- and living related transplantation. OLT should also be offered to elderly patients. Careful evaluation and patient selection results in good patient and graft survival after transplantation, which is comparable to that in with younger recipients.

[Mesohepatectomy-an alternative to extended hepatectomy in the treatment of central liver tumors]. / Mesohepatektomie. Eine Alternative zur erweiterten Hemihepatektomie bei zentralen Lebertumoren.

Mesohepatectomy was performed in seven patients with a primary or secondary central liver tumor. We describe the surgical procedure for mesohepatectomy (removal of segments IVa/IVb/V/VIII +/- I) in the treatment of central hepatic tumors. This technically demanding but safe approach requires careful vascular dissection to maintain blood supply and venous drainage of the two remaining liver parts. Mesohepatectomy results in one or two large resection planes bearing a considerable risk of parenchymal necrosis or biliary leakage. Its major advantage over extended hepatectomy is the preservation of functioning liver tissue. Thus, the risk of postoperative liver failure is reduced and, in case of intrahepatic recurrence, the chance for repeat hepatectomy improved. Mesohepatectomy should be considered in selected cases of central liver tumors in which extended resection would be associated with a high risk of liver insufficiency.

Terlipressin and gelafundin: safe therapy of hepatorenal syndrome.

BACKGROUND AND AIM: Hepatorenal syndrome (HRS) occurs in about 20 % of patients with liver cirrhosis and ascites and is characterized by intensive renal vasoconstriction, low glomerular filtration rate but preserved tubular function and normal renal histology. The potential of terlipressin and albumin to reverse HRS after a time period of 14 days has already been shown. However, intravenous albumin is expensive (approximately 25 per 50 ml 20% albumin in Germany) and has limited availability in some settings. Therefore we used an artificial plasma substitute, Gelatinepolysuccinat, which is less expensive (approximately 12 per 500 ml). The aim of our present study was to examine the effects of terlipressin and Gelatinepolysuccinat on renal function and hemodynamics in a time period of six days. METHODS AND PATIENTS: Seven consecutive patients with cirrhosis and hepatorenal syndrome were included in a pilot study of terlipressin (6 mg /24 h iv) therapy associated with i.v. Gelatinepolysuccinat (Gelafundin 4% Infusionslösung, Company Braun, Mw: 30 000 D). RESULTS: In five of the seven patients treatment was associated with a marked reduction of serum creatinine after six days (3.85 +/- 0.44 mg/dl vs.1.9 +/- 0.32 mg/dl; p< 0.018). Creatinine clearance improved (20 +/- 8.8 ml/min vs. 43 +/- 11.7 ml/min; p<0.12). There was a remarkable improvement in circulatory function in all patients, with an increase in mean arterial pressure (58+/-4.4 mmHg vs. 75 +/- 4.5 mmHg, p< 0.001). No patient developed signs of intestinal, myocardial or distal ischemia. CONCLUSIONS: Terlipressin and Gelatinepolysuccinat appear to be a safe and effective treatment of hepatorenal syndrome.

Feasibility of veno-venous bypass surgery using leukocyte adhesion filters during abdominal surgery in a porcine model.

During oncologic surgery, manipulation of tumour tissue is almost unpreventable; liver resection even carries a higher risk of tumour cell dissemination into venous blood. Under in vitro conditions, a tumour cell reducing effect of some leukocyte adhesion filter systems has been shown. In a preclinical porcine model, these filters were used as integrated parts of a veno-venous bypass system used for liver surgery, run by a biopump. Practicability, handling and safety aspects of the filter system were analysed; the system was easy and safe to handle, and treated animals survived without any complications. For the future, effectiveness of the tumour cell depletion has to be examined in further experimental and clinical studies.

Postoperative ICU management in liver transplant patients.

The unique pathophysiology of end-stage liver disease (ESLD) has important implications on critical care treatment after liver transplantation. To determine hemodynamic parameters and responses, each patient must be carefully evaluated for the individual clinical appearance of cirrhosis and portal hypertension. Although data are limited, recent progress in the treatment of ESLD and its complications, such as hepatorenal syndrome (HRS), portopulmonary hypertension (PPH), and hepatopulmonary syndrome (HPS) is evident. The improved understanding of the pathophysiology of ESLD has resulted in novel treatments and approaches to the problems that emerge as patients get critically ill or undergo orthotopic liver transplantation (OLT). These issues become much more relevant with increased adult-to-adult living donor liver transplantation, where the scheduled operation allows a precise preoperative management in an Intensive Care Unit (ICU).

[Intraoperative radiotherapy in Germany]. / Aktueller Stand der intraoperativen Strahlentherapie in Deutschland.

BACKGROUND: Intraoperative radiotherapy (IORT) represents an attractive method for local tumour control after surgical resection. IORT was introduced into multimodal treatment protocols in the 1980s. Aim of this study was to analyse the actual clinical and scientific activity of IORT in Germany. METHODS: Questionnaires were sent to 102 centres in Germany. The analysis was focussed on indications in general surgery including bone tumours to evaluate the activity of IORT. The literature was analysed by a medline search for the years 1975 to 2001. RESULTS: Questionnaires were answered by 92% of the centres. 24 departments are working with IORT in Germany (16 of them are university hospitals). Main Indications for IORT treatment are rectum carcinoma and soft tissue sarcoma. Furthermore, IORT is used in patients suffering from gastric, pancreatic and bile duct malignancies. Some IORT programs are also targeting on patients with head and neck malignancies and brain tumours. German institutions published within the last 5 years about 14% of all " Medline"-listed publications concerning IORT. CONCLUSION: There is an profound activity of IORT in Germany, which is concentrated on a few centres. A need for better national and international cooperation of centres performing IORT for clinical trials and to collect significant numbers of patients seems to be evident.