Influence of Deceased Donor and Pretransplant Recipient Parameters on Early Overall Kidney Graft-Survival in Germany.

Background. Scarcity of grafts for kidney transplantation (KTX) caused an increased consideration of deceased donors with substantial risk factors. There is no agreement on which ones are detrimental for overall graft-survival. Therefore, we investigated in a nationwide multicentre study the impact of donor and recipient related risks known before KTX on graft-survival based on the original data used for allocation and graft acceptance. Methods. A nationwide deidentified multicenter study-database was created of data concerning kidneys donated and transplanted in Germany between 2006 and 2008 as provided by the national organ procurement organization (Deutsche Stiftung Organtransplantation) and BQS Institute. Multiple Cox regression (significance level 5%, hazard ratio [95% CI]) was conducted (n = 4411, isolated KTX). Results. Risk factors associated with graft-survival were donor age (1.020 [1.013-1.027] per year), donor size (0.985 [0.977-0.993] per cm), donor's creatinine at admission (1.002 [1.001-1.004] per µmol/L), donor treatment with catecholamine (0.757 [0.635-0.901]), and reduced graft-quality at procurement (1.549 [1.217-1.973]), as well as recipient age (1.012 [1.003-1.021] per year), actual panel reactive antibodies (1.007 [1.002-1.011] per percent), retransplantation (1.850 [1.484-2.306]), recipient's cardiovascular comorbidity (1.436 [1.212-1.701]), and use of IL2-receptor antibodies for induction (0.741 [0.619-0.887]). Conclusion. Some donor characteristics persist to impact graft-survival (e.g., age) while the effect of others could be mitigated by elaborate donor-recipient match and care.

The joint impact of donor and recipient parameters on the outcome of heart transplantation in Germany after graft allocation.

Organ shortage in heart transplantation (HTx) results in increased use of grafts from donors with substantial risk factors. It is discussed controversially which donor characteristics may be detrimental. Therefore, we evaluated the joint impact of donor- and patient-related risk factors in HTx on patient survival by multiple analysis in a nationwide multicentre study after donor selection was carried out. The research database consists of data concerning hearts donated and transplanted in Germany between 2006 and 2008 as provided by Deutsche Stiftung Organtransplantation and the BQS Institute. Multiple Cox regression (significance level 5%, hazard ratio [95% CI]) was conducted (n = 774, recipient age ≥ 18 years). Survival was significantly decreased by donor age (1.021 [1.008-1.035] per year), nontraumatic cause of death (1.481 [1.079-2.034]), troponin >0.1 ng/ml (2.075 [1.473-2.921]), ischaemia time (1.197 [1.041-1.373] per hour), recipient age (1.017 [1.002-1.031] per year) and in recipients with pulmonary vascular resistance ≥ 320 dyn*s*cm(-5) (1.761 [1.115-2.781]), with ventilator dependency (3.174 [2.211-6.340]) or complex previous heart surgery (1.763 [1.270-2.449]). After donor selection had been conducted, multiple Cox regression revealed donor age, nontraumatic cause of death, troponin and ischaemia time as well as recipient age, pulmonary hypertension, ventilator dependency and previous complex heart surgery as limiting risk factors concerning patient survival.

Extracorporeal tumor cell filtration during extended liver surgery: first clinical use of leukocyte depletion filters--case series.

BACKGROUND: During oncologic surgery, intraoperative manipulation of tumor tissue is almost unpreventable and causes a high risk of tumor cell dissemination into venous blood. A tumor cell-reducing effect of leukocyte adhesion filter systems has been shown under in vitro conditions. METHODS: In a first clinical attempt, leukocyte adhesion filters were integrated into veno-venous bypass systems in four patients undergoing extended liver surgery for secondary hepatic malignancies.Practicability, handling, and safety aspects as well as potency of cell removal and clinical side effects of the filter system were analyzed. RESULTS: All patients tolerated the application of the system without problems during operative and postoperative follow-up. Immunohistochemical staining of perioperative blood samples detected cytokeratin positive (CK+) cells in three cases during the hepatic mobilization. CONCLUSIONS: Effectiveness of CK+ cell depletion and safety of the procedure was shown. The presented surgical technique represents a safe and innovative tool; however, clinical significance has to be examined in a larger patient cohort.

The effect of education on the attitude of medical students towards organ donation.

BACKGROUND: The persisting shortage of organs for transplantation could be reduced by increasing the willingness to donate organs. An appropriate education and a positive attitude of medical students and future physicians towards organ donation may have a positive impact on the attitudes of the general public. MATERIAL/METHODS: During the summer semester 2010 we conducted a voluntary educational intervention study concerning organ donation among medical students in the course of the main surgery lecture at the University of Essen, Germany. RESULTS: The survey comprised 94 questionnaires. At the beginning of the lecture there were 67% of organ donor card carriers among the students. An additional 20% imagined they might carry an organ donor card in the future. 37% needed more information regarding organ donation. After the lecture 13% were still not willing to carry an organ donor card in the future. 18% of the students required further information. 42% of the students rated their attitude towards organ donation to be influenced positively by the lecture, 57% of the students stated there was no influence. One student documented a negative influence by the lecture towards organ donation. CONCLUSIONS: Well-directed interventions are needed to sensitize young adults to the topic of organ donation. Better understanding of medical students and future physicians in the field of organ donation will help them to become disseminators for this important topic in our society.

Joint impact of donor and recipient parameters on the outcome of liver transplantation in Germany.

BACKGROUND: The shortage of donor organs in Germany has led to the use of organs from donors with extended donor criteria (EDC). EDC have been defined on the basis of expert opinions, but their clinical relevance is controversial. This may cause loss of organs otherwise available for transplantation. We evaluated the impact of donor and recipient factors in liver transplants on patient and graft survival in a nationwide multicenter analysis, with special focus on EDC and donor risk index. METHODS: A database was created from data on livers donated and transplanted in Germany between 2006 and 2008 as provided by Deutsche Stiftung Organ transplantation and BQS Institute. Cox regression (significance level 5%, risk ratio [95% confidence interval]) was used for calculating the impact on patient survival (n=2095) and on graft survival (n=2175). RESULTS: Patient and graft survival were significantly affected only by donor age (1.012 and 1.011/year), recipient age (1.019 and 1.014/year), creatinine (1.248 and 1.205/mg/dL), bilirubin (1.022 and 1.023/mg/dL), and high urgency status (1.783 and 1.809). Inferior organ quality resulted in lower graft survival (1.243) and donor history of smoking in lower patient survival (1.249). CONCLUSION: Multiple Cox regression revealed no significant impact of EDC or donor risk index on patient and graft survival except for donor age after donor selection at recovery. Among recipient variables, only age, creatinine and bilirubin, and high urgency status were associated with poorer outcome.

Survival of patients with synchronous and metachronous colorectal liver metastases--is there a difference?

BACKGROUND: The aim of this study was to compare outcomes in patients with synchronous and metachronous colorectal liver metastases, with special emphasis on prognostic determinants. STUDY DESIGN: We analyzed prospectively collected data on 101 patients with synchronous metastases (group A) who were treated surgically during the time period from April 1998 to December 2006 in regard to overall and disease-free survival, impact of chemotherapy, as well as several serum parameters. A group of patients with metachronous colorectal liver metastases (group B) was considered for baseline comparison. RESULTS: Twenty-three patients in group A received only an explorative laparotomy. Surgical treatment included right hepatectomy (n = 7), left hepatectomy (n = 5), right trisectionectomy (n = 10), left trisectionectomy (n = 1), left lateral resection (n = 11), and sectionectomy (n = 44). Thirty-day mortality was 3%. Morbidity was observed in 10% of the patients. One-, 3-, and 5-year overall survival rates for synchronous metastases were 86%, 68%, and 47%, respectively. The corresponding rates for metachronous metastases were 94%, 68%, and 39% (p > 0.05). Disease free survival was 74%, 42%, and 33% in group A versus 84%, 62%, and 13% in group B (p = 0.28). There was no difference in survival between patients receiving neoadjuvant chemotherapy and no chemotherapy (p > 0.05). Out of all serum parameters, carcinoembryonic antigen levels were a negative predictor for overall and disease-free survival only. CONCLUSIONS: Patients with synchronous colorectal liver metastases had a similar 5-year overall and disease-free survival, which corresponds to patients with metachronous metastases. The impact of neoadjuvant chemotherapy in patients with synchronous metastases needs to be further clarified.

Value of staging laparoscopy for multimodal therapy planning in esophago-gastric cancer.

The importance of multimodal treatment for advanced esophago-gastric cancer has contributed to the development of more accurate preoperative staging strategies. The impact of staging laparoscopy and cytology after conventional staging is evaluated in this study. Staging laparoscopy was performed in 125 patients with potentially resectable cancer of the distal esophagus or gastric cancer. Results were registered separately on a database according to the TNM classification of the International Union Against Cancer (UICC). Laparoscopy changed TNM classification in 46 cases. Explorative laparoscopy resulted in up-staging concerning the N-factor (n = 15) and M-factor (n = 28). Downstaging of the T-factor was recorded in three cases. Cytologic examination gave no additional information in our series. Our experience suggests a clear benefit of laparoscopy in staging of patients with distal esophagus or gastric malignancy. Laparoscopy is a safe and effective staging modality, avoiding unnecessary laparotomies and providing new means of directing appropriate treatment strategy.

Anesthesia for cardiovascular interventions and magnetic resonance imaging in pigs.

Large animal models are still required for many experimental purposes. The aim of the current study was to define a viable narcotic procedure for experimental cardiovascular interventions and imaging in pigs. A total of 32 domestic pigs were used. Animals received propofol, midazolam, and fentanyl as continuous intravenous infusion anesthesia for complex vascular interventions, angiographic X-ray imaging, and magnetic resonance imaging (MRI). Anesthesia was maintained for 6 to 10 h. The initial hourly doses were 2.29 mg/kg of propofol, 1.14 mg/kg of midazolam, and 0.009 mg/kg of fentanyl, with controlled ventilation. Anesthesia, interventions, imaging, periods of apnea of as long as 2 min, and transportation were well-tolerated. Stress-induced arrhythmias were not noted, and artifact-free imaging was achieved. The combination of propofol, midazolam, and fentanyl is well-suited for experimental angiographic interventional studies, experimental cardiovascular MRI, and MR-guided interventions in pigs.

Method of intracranial pressure monitoring and cerebrospinal fluid sampling in swine.

Cerebral oedema and encephalopathy have been noted to occur frequently in patients severely ill or dying after trauma, ischaemia, infections or even metabolic disorders. The objective of the present study was to establish continuous monitoring of the intracranial pressure (ICP) and sampling of cerebrospinal fluid (CSF) for further investigations in swine. ICP monitoring was established in eight pigs by using a ventricular drainage system, implemented after paramedian trepanation of the os frontale. CSF and serum samples were taken for measurement of the levels of glucose and protein. Operating time was 21+/-8 min for the trepanation until ICP monitoring was performed. No complications occurred during surgery. Continuous monitoring of ICP and CSF sampling was easy to perform, and without any side-effects in any animal. At autopsy, no iatrogenic lesions were found and monitoring catheters were still in place. For several types of research requiring ICP monitoring and sampling of CSF, this method can be used successfully.

Split liver transplantation for hepatocellular carcinoma.

BACKGROUND/AIMS: Liver transplantation (LTx) is recognized as the treatment of choice for small hepatocellular carcinomas (HCC) in patients with end-stage liver failure. However, because of limited organ availability, not all those who qualify can benefit from full-size LTx. METHODOLOGY: Over a 28-month period, we transplanted 6 deceased donor split liver allografts in stable recipients with HCC and cirrhosis. RESULTS: There were 5 men and one woman with a median age of 60 years. Median waiting time to LTx was 82 days. Extended right split grafts (segments I, IV-VIII) were transplanted in 5 patients. One patient received a right split graft. In situ harvesting was performed in 4 instances and ex situ in the remaining 2. Median cold ischemia time was 10 hours. Primary non-function was not observed. Median intensive care unit stay was 4 days. There were neither vascular nor biliary complications. The postoperative course was uneventful in half of the patients. Two patients were re-operated because of an abscess caused by a liver necrosis in the marginal zone of segment IV. One patient died for reasons unrelated to liver function or to the surgical intervention. The remaining 5 patients are alive after a median follow-up of 20 months. CONCLUSIONS: Deceased donor split LTx constitutes an additional option for patients with HCC and cirrhosis. The potential risks of using "split livers" as well as the potential benefits of transplanting patients unlikely to survive the waiting list period must be evaluated on an individual basis.

Portopulmonary hypertension in the early phase following liver transplantation.

BACKGROUND: Portopulmonary hypertension (PPH) is a severe complication of liver cirrhosis, which poses a high risk for postliver transplantation (LT) mortality. In most liver transplant centers, severe PPH is viewed as an absolute contraindication for LT, but recent reports challenge this. The purpose of our study was to determine the incidence of PPH, its influence on the 30-day mortality rate following LT and to determine the sensitivity and specificity of Doppler echocardiography and electrocardiography as noninvasive tools to determine PPH. METHODS: We studied 74 consecutive patients that underwent LT between February 2004 and November 2005. Pulmonary arterial pressure and cardiac index were repeatedly determined during surgery and postoperatively. PPH was defined as mild (mean pulmonary arterial pressure (MPAP) 25-35 mm Hg), moderate (MPAP of 35-45 mm Hg) and as severe (MPAP >45 mm Hg). RESULTS: The total incidence of PPH was 31% (16 mild, 5 moderate, and 2 severe). There was a tendency towards increased 30-day mortality rate in patients with PPH compared to controls (22% vs. 12%, P=0.1). However, the two patients with the most severe PPH survived. The duration of ventilation and total stay at the intensive care unit did not differ significantly between groups. The positive predictive value of Doppler echocardiography for PPH was 39% and the negative predictive value 90%. CONCLUSIONS: Mild pulmonary hypertension is common in patients with liver failure, whereas moderate and severe hypertension is not. Severe PPH should not be considered as absolute contraindication for LT.

Does PEEP impair the hepatic outflow in patients following liver transplantation?

OBJECTIVE: Evaluation of the impact of end-expiratory pressure (PEEP) ventilation on venous liver outflow, portal vein, and hepatic artery flows as well as systemic hemodynamics in patients following liver transplantation (LT). DESIGN: Prospective, interventional patient study. SETTING: University hospital intensive care unit. PATIENTS: 65 consecutive patients after LT. INTERVENTIONS: All patients were intubated and mechanically ventilated with biphasic positive airway pressure (BIPAP). The effects of three levels of PEEP (0, 5, and 10 mbar) applied at random order on hepatic inflow and outflow were studied in the immediate postoperative period. MEASUREMENT AND RESULTS: Central venous-, arterial pressure, and cardiac index was recorded from every patient at three different PEEP levels (0, 5, and 10 mbar). Simultaneously, flow velocities in the hepatic-, portal vein, and hepatic artery were determined by Doppler ultrasound. PEEP of 10 mbar significantly increased central venous pressure in comparison with zero PEEP. Mean arterial pressure and cardiac index was not influenced. Hepatic inflow and outflow of the transplanted livers were not impaired by any of the used PEEP levels. CONCLUSIONS: BIPAP ventilation with PEEP levels up to 10 mbar does not affect systemic hemodynamics. Furthermore, neither venous outflow nor portal venous or hepatic artery inflow of the liver are impaired at PEEP levels up to 10 mbar immediately following liver transplantation. Although these results suggest that PEEP ventilation up to 10 mbar does not affect liver hemodynamics, further studies are needed to determine whether these findings could be confirmed for a longer ventilation period with PEEP.

Neurological complications after cadaveric and living donor liver transplantation.

Problems related to the central nervous system have a major impact on survival and quality of life. The aim of this retrospective study was to evaluate the incidence of neurological complications after liver transplantation (LT), including both cadaveric and living donor liver transplantation. Between April 2001 and March 2004 174 patients (120 cadaveric liver transplantations, 54 living donor transplantations) were admitted to our intensive care after liver transplantation. Of the transplanted patients 24.7% developed neurological complications. These patients' stay in the intensive care (14.2 +/- 17.2 days) was much longer than that of all admitted patients (8.4 +/- 10.5 days, p < 0.05). The most common neurological complications were encephalopathy (72.1%) and seizures (11.6 %). The incidence of neurological complications in living donor liver transplanted patients was significantly lower than in cadaveric transplantation patients (20.4% vs 26.7 %). The cold ischemia time in living donor transplanted patients was significantly shorter in comparison with cadaveric transplanted patients (215 +/- 119.3 vs. 383.7 +/- 214.7). The survival rate after liver transplantation of patients with neurological complications was lower than that of patients without, but not significantly different (79.1 % vs. 82.4%, p > 0.05). The incidence of neurological symptoms was found to be similar between the patients treated with cyclosporine (25%) and tacrolimus (23.8 %) in this study. In conclusion, there was a high incidence of neurological complications after LT, prolonging the patients' stay in intensive care significantly. The major neurological manifestation in our patients was encephalopathy followed by seizures. Living donor liver transplantation was associated with a significantly lower incidence of neurological complications compared with patients who had received a cadaveric graft. This might be due to the good quality of the organ and the much shorter cold ischemia time of the graft when the donor was alive.

General handling and anesthesia for experimental surgery in pigs.

The pig is a common large animal for experimental settings in many fields of surgery. In experimental surgery, there is a need for different narcotic procedures depending on the complexity of the surgical investigation. Narcotic procedures have to be safe, easy to handle, and should not influence the experimental results. We hereby present important aspects of handling and narcotic procedures for pigs. The aim of this publication is to supply an introduction for young surgical investigators who are planning or already have started investigations using pigs as an experimental animal. This publication is based on our institutional experience of narcotic and surgical procedures in more than 400 cases.

Impact of virtual tumor resection and computer-assisted risk analysis on operation planning and intraoperative strategy in major hepatic resection.

HYPOTHESIS: Currently, standard planning for hepatic resection is based on the schematic description of the functional anatomy of the liver according to Couinaud, and on the evaluation of 2-dimensional computed tomographic imaging of the liver. Recent developments in image-based computer assistance allow patients' individual functional liver anatomy to be computed from mathematical analysis of standard multidetector computed tomographic scans. An intended resection can be performed virtually under realistic anatomic conditions, and the influence of different resection planes on blood supply and drainage within the remaining liver parenchyma can be calculated by a computer-assisted risk analysis. We evaluated the impact of computer-assisted risk analysis on operation planning for major hepatectomies, in particular on extent of resection or need for vascular reconstruction. DESIGN: Prospective cohort study. SETTING: Academic tertiary care referral center. PATIENTS: Twenty-five consecutive patients admitted to the hospital for major hepatectomy, of whom 4 had tumors deemed unresectable by both methods. INTERVENTIONS: Two-dimensional computed tomography was used to calculate the volume of the future liver remnant with the intended resection line manually determined, and then the volume of the future liver remnant was calculated again by computer-assisted risk analysis as the remaining liver volume not being devascularized but having both portal venous blood supply and hepatic venous drainage. MAIN OUTCOME MEASURES: The difference between the remaining functional liver volumes calculated by the 2 methods. RESULTS: The deviation between liver volumes determined by 2-dimensional computed tomography and by computer-assisted risk analysis was less than 20% in 14 of 21 patients, between 20% and 30% in 3, between 30% and 40% in 2, and 41% and 43% in 1 patient each. The most extensive deviations were found in extended left hepatectomy or when left hepatectomy was combined with additional wedge resection in the right lobe. In 7 cases, all with a deviation greater than 20%, the results of computer-assisted risk analysis led to a change of operation planning with regard to the extent of resection (n = 3) or the need for vascular reconstruction (n = 4), although in 1 of these cases resection was not performed because of peritoneal carcinomatosis. CONCLUSIONS: Image-based computer assistance allows for areas at risk for devascularization or venous congestion to be identified and precisely calculated before resection. In selected cases with small liver remnants, operation planning may be improved substantially by preoperative computer-assisted risk analysis.

Preoperative donor liver biopsy for adult living donor liver transplantation: risks and benefits.

The role of liver biopsy (LB) in donor selection for adult living donor liver transplantation remains controversial, since the procedure is associated with additional potential risks for the donor. From April 1998 to August 2004, 730 potential living donors for 337 adult recipients underwent our multistep evaluation program. In 144 candidates, LB was performed. LB was obtained in a percutaneous ultrasound-guided fashion by means of Menghini needle (32 cases) or Tru-cut needle (112 cases). The biopsy specimen was preserved in 5% formalin and processed with hematoxylin & eosin-stained sections. Thirty-one (21%) of 144 candidates who underwent an LB had a positive finding at histological examination that induced their exclusion from donation, of whom 21 had liver steatosis of varying kind and grade (10%-80%) and 10 had a nonsteatotic hepatopathy (non-A-D hepatitis in 6 cases, diffuse granulomatosis in 2, schistosomiasis in 1, fibrosis in 1). The only observed major complications related to LB were 2 intraparenchymal haematomas, both of which resolved spontaneously within a few months. In conclusion, based on these findings, we believe that preoperative LB in the donor selection for adult LDLT is necessary, once the initial donor screening and noninvasive evaluation is complete. Because other screening modalities can be unreliable, without preoperative LB a fraction of potential donors will be operated on inappropriately, risking both donor and recipient. The main objective of LB should be to ensure the donor's safety more than the preservation of the graft function.

Outcome after orthotopic liver transplantation in five HIV-infected patients with virus hepatitis-induced cirrhosis.

BACKGROUND: We report on our experiences with orthotopic liver transplantation (OLT) in HIV-infected patients. Between July 1998 and October 2001, five HIV-infected patients underwent OLT because of virus-induced liver cirrhosis. One patient suffered from hepatitis B virus (HBV)-, three patients from hepatitis C virus (HCV)- and one patient from HCV/HBV/HDV-related cirrhosis (HDV, hepatitis D virus). The mean duration of HIV infection was 15 years. Patients were prospectively followed up with a mean duration of 25.6 months. RESULTS: Three patients died 3, 10 and 31 months after OLT, respectively, due to graft failure. The causes of graft failure were: recurrent thrombosis of the hepatic artery, HCV-associated cholestatic hepatitis and chemotherapy-induced liver damage due to Hodgkin's disease, which was diagnosed 17 months after OLT, in addition to chronic HCV disease. The two survivors show a stable liver function and non-progredient HIV infection under antiretroviral therapy 61 and 23 months after OLT, respectively. CONCLUSIONS: A medium- or even long-term survival after OLT can be achieved in HIV-infected patients without progression of HIV disease under antiretroviral therapy. However, in our study three out of five patients died due to graft failure. Therefore, prognostic criteria have to be defined for the selection of HIV-infected patients, who may benefit from OLT.