Abstract: ABSTRACT: Introduction Inflammatory pseudotumor of the liver represents a fairly uncommon pathology. Although it is a benign tumor, the correct diagnosis can be missed. Case presentation We report the case of a 55-year-old Caucasian man, who presented with a one-month history of abdominal pain and weight loss. He was diagnosed with a primary liver tumor by computed tomography and magnetic resonance imaging. Alpha-fetoprotein levels ranged within normal limits. A right posterior sectorectomy was performed. Histopathology revealed an inflammatory pseudotumor of the liver. Our patient remains in good condition one year later. Conclusion Although inflammatory pseudotumor of the liver is usually a benign process, controversy regarding its management still exists. With this case report we review the existing literature and consider hepatectomy as a safe treatment approach.
Abstract: PURPOSE: Technetium(99m) sestamibi (MIBI) has poor sensitivity and specificity when applied to patients with secondary hyperparathyroidism. We investigated whether the combination of MIBI with preoperative parameters increased its accuracy. PATIENTS AND METHODS: This prospective study of 453 consecutive patients with secondary hyperparathyroidism who underwent parathyroidectomy (bilateral neck exploration) included preoperative MIBI scintigraphy compared with intraoperative and histopathology findings. Four patient groups were comprised according to the results: true positivity (TP), true negativity (TN), false positivity (FP), and false negativity (FN). RESULTS: MIBI scintigraphy sensitivity, specificity, positive predictive value, and negative predictive value were 66.4%, 50%, 76.3%, and 37.9%, respectively. For the TP group, mean age and mean parathormone (PTH) value were 56 years and 754, respectively. The binary logistic regression for the prediction (1) or not (2) of TP was as follows: 0.138 + (-.011) * age + 0.001 * PTH (P = .012). For the TN group, the mean age and mean phosphate value were 49 years and 5.24, respectively. The binary logistic regression for the prediction (1) versus not (2) of the TN was as follows: -1.463 + age * (-.029) + phosphate * 0.233 (P = .012). CONCLUSION: MIBI accuracy in patients with secondary hyperparathyroidism was increased when combined with other preoperative parameters. The sensitivity was increased as patients were older and the PTH levels were lower. The specificity was increased as patients were younger and the phosphate levels were lower.
Abstract: We retrospectively evaluated the use of double-j stent and the incidence of urological complications in 2 groups of patients who received a kidney transplant. From January 2005 to September 2007 we studied 172 patients receiving kidney transplants, 65 and 107 from living and cadaver donors, respectively. From the 172 patients, a total of 34 were excluded due to ureterostomy or Politano-Leadbetter ureterovesical anastomosis. Another 21 patients were excluded from the study due to graft loss due to acute or hyperacute rejection, cytomegalovirus (CMV) infection, or vascular complication. The remaining patients were divided into 2 groups: group A (44 patients) and B (73 patients) with versus without the use of a double-j-stent, respectively. The 2 groups were comparable in terms of donor and recipient gender, ischemia time, and delayed graft function. We failed to observes significant differences between the 2 groups in mean hospital stay (23 +/- 9 and 19 +/- 9), urinary leak (2.3% and 4.1%), and urinary tract infection (20.4% and 19.2%), among groups A and B, respectively. The only difference observed concerned the gravity of the urinary leak; no surgical intervention was needed among the double-j stent group versus 2 patients demanding ureterovesical reconstruction in the nonstent group. In conclusion, our data suggested that the routine use of a double-j stent for ureterovesical anastomosis neither significantly increased urinary tract infection rates, nor decreased the incidence of urinary leaks, but may decrease the gravity of the latter as evidenced by the need for surgical intervention.
Abstract: We present a case of bilateral Morgagni hernia in a 68-year-old male with an intermittent history of progressive onset of breath shortness and occasional cardiac arrhythmias. Diagnosis was made by clinical examination and the findings in a plain chest radiograph and was confirmed by computed tomography scan. The patient was operated electively and subjected to a transabdominal approach. A bilateral subcostal incision revealed a large right side anterior diaphragmatic defect with a hernia containing the ascending colon, the majority of the transverse colon and a huge amount of omentum. Also a second smaller defect was found on the left side with no hernia inside. After large bowel and omentum had been taken down to the peritoneal cavity, both defects were primarily closed using interrupted nylon sutures without the use of a mesh. The patient recovered very well, had an uneventful postoperative course and was released on the 5th postoperative day. 15-month follow-up failed to reveal any signs of recurrence.
Abstract: BACKGROUND: Liver transplantation represents the main treatment for alcoholic cirrhosis. The goal of this article is to review the results of liver transplantation for alcoholic cirrhosis in Greece over the last 2 decades. METHODS: Among 247 patients who underwent liver transplantation between 1991 and 2007, 34 (13.7%) experienced alcoholic cirrhosis as the primary diagnosis. We reviewed their demographic data, stage of liver disease, and outcomes regarding survival via a Kaplan-Meier curve. Also we analyzed the causes of death and the postoperative complications. RESULTS: Mean Model for End-Stage Liver Disease (MELD) score was 18.4. Other diagnoses included hepatitis C virus (HCV; 23.5%), hepatitis B virus (HBV; 14.7%), and hepatocellular carcinoma (8.8%). Eleven patients died the most frequent causes being primary graft nonfunction (n = 3), hepatic artery thrombosis (n = 2), sepsis (n = 2), and portal vein thrombosis (n = 2). Complications included rejection (32.4%), infection (26.5%), hepatic graft dysfunction (11.8%), and recurrent HCV, recurrent HBV, and renal failure (8.8% each). Recurrence of alcoholism was observed in 3 patients (8.8%) with mild effects on liver function tests. There has been a significant increase in the number of liver transplantations for alcoholic cirrhosis in the last 6 years, namely 25 patients versus 9 in the previous 10 years. CONCLUSIONS: We observed a significant increase in the frequency of alcoholic cirrhosis leading to liver transplantation in the last several years in Greece.
Abstract: The use of primary human liver cells obtained from discarded donor organs is increasingly favored for cell-based extracorporeal liver support systems. However, as cryopreservation of primary human hepatocytes causes a significant loss of metabolic activity, the transport of bioreactors with viable liver cells is required. The aim of this study was to evaluate the impact of two major potential threats to viable cells during transport: temperature changes and mechanical stress.
Abstract: To enable extracorporeal liver support based on the use of primary liver cells, culture models supporting the maintenance of cell integrity and function in vitro are required. In this study the cell organization and ultrastructure of primary porcine hepatocytes cocultured with nonparenchymal cells in three-dimensional high-density bioreactors were analyzed after 10, 20, and 30 days of culture by immunohistochemistry and transmission electron microscopy. Biochemical data showed that metabolic activity of the cells in the system was relatively stable over at least 20 days. Immunohistochemical studies were performed in comparison with donor organ biopsies. They showed that hepatocytes and nonparenchymal cells reaggregated in bioreactors, forming structures partly resembling natural liver parenchyma. Bile duct-like structures characterized by cytokeratin 7 (CK-7) immunoreactivity (IR) were regularly detected. Nonparenchymal cells (vimentin IR) formed sinusoidal-like structures within parenchymal cell aggregates. Proliferative activity (Ki-67 IR) increased over time. The detection of collagen I and laminin indicated the production of extracellular matrix components within bioreactors. The results showed that primary liver cell reorganization and long-term maintenance of their differentiated state were achieved within the bioreactors The findings on cell proliferation indicated that the culture model is also of interest for further in vitro studies on cell regeneration and tissue formation.
Abstract: METHODS: Following liver transplantation, a 26-year old female suffered from primary non-function of the transplant. The patient was subsequently treated with a modular extracorporeal liver support concept until a suitable organ became available. A bioreactor was charged with human liver cells, obtained from a discarded cadaveric graft (470 g, viability: 60%). The bioreactor was integrated into an extracorporeal circuit with continuous single pass albumin dialysis and continuous veno-venuous hemodiafiltration for detoxification and fluid reduction. RESULTS: Over the total system application time of 79 h, a significant reduction of the plasma levels of total bilirubin (21.1 mg/dl at start, 10.1 mg/dl at end of therapy) and ammonia (100 versus 22.7 micromol/l) was achieved. During treatment the patient's neurological status significantly improved from coma stage IV to I permitting extubation. Recovery of kidney function with a urine output of 1325 ml/24 h compared to 45 ml/24 h prior to system application, was noted. Over the treatment period, an improvement of coagulation status was observed. Adverse events were absent. CONCLUSIONS: This first successful clinical treatment of a patient with liver failure suggests that a modular approach combining both primary human liver cell bioreactor technology and detoxification methods is promising.
Abstract: The objective of this study was to evaluate the feasibility and safety of a hybrid liver support system with extracorporeal plasma separation and bioreactor perfusion in patients with acute liver failure (ALF) who had already fulfilled the criteria for high urgency liver transplantation (LTx). Eight patients (one male, seven female) were treated in terms of bridging to transplantation. The mean age was 36.5 yr (range 20 to 58). Etiology of liver failure was drug-related in two patients, hepatitis B infection in three patients, and unknown for three patients. The bioreactors were charged with primary liver cells from specific pathogen-free pigs. Cell viability varied between 91 and 98%. Continuous liver support treatment over a period of 8 to 46 h (mean 27.3 h) was safely performed and well-tolerated by all patients. No complications associated with the therapy were observed during the follow-up period. Thrombocytopenia was considered to be an effect of the plasma separation. Subsequently, all patients were transplanted successfully and were observed over at least 3 yr with an organ and patient survival rate of 100%. Screening of patient's sera for antibodies specific for porcine endogenous retroviruses (PERVs) showed no reactivity--either prior to application of the system, or after extracorporeal treatment. The results encourage us to continue the development of the technology, and further studies appear to be justified. The bioreactor technology has been integrated into a modular extracorporeal liver support (MELS) system, combining biologic liver support with artificial detoxification technology.
Abstract: Cell-based extracorporeal liver support is an option to assist or replace the failing organ until regeneration or until transplantation can be performed. The use of porcine cells or tumor cell lines is controversial. Primary human liver cells, obtained from explanted organs found to be unsuitable for transplantation, are a desirable cell source as they perform human metabolism and regulation. The Modular Extracorporeal Liver Support (MELS) concept combines different extracorporeal therapy units, tailored to suit the individual and intra-individual clinical needs of the patient. A multi-compartment bioreactor (CellModule) is loaded with human liver cells obtained by 5-step collagenase liver perfusion. A cell mass of 400 g - 600 g enables the clinical application of a liver lobe equivalent hybrid organ. A detoxification module enables single pass albumin-dialysis via a standard high-flux dialysis filter, and continuous veno-venuous hemodiafiltration may be included if required. Cells from 54 human livers have been isolated (donor age: 56 +/- 13 years, liver weight: 1862 +/- 556 g resulting in a viability of 55.0 +/- 15.9%). These grafts were not suitable for LTx, due to steatosis (54%), cirrhosis (15%), fibrosis (9%), and other reasons (22%). Out of 36 prepared bioreactors, 10 were clinically used to treat 8 patients with liver failure. The overall treatment time was 7-144 hours. No adverse events were observed. Initial clinical applications of the bioreactor evidenced the technical feasibility and safety of the system.
Abstract: Aim of the study was to evaluate a hybrid liver support system in a porcine model of acute liver failure, after hepatectomy. Pigs with a body weight of 70+/-18 kg underwent total hepatectomy and porto-cavo-caval shunting as well as ligation of the bile duct and the hepatic artery. Control animals were connected to the system (including capillary membrane plasma separation) containing a four compartment bioreactor with integral oxygenation and decentralized mass exchange but without liver cells. The treatment group received hybrid liver support with the same system including 370+/-42 g primary isolated porcine parenchymal liver cells in co-culture with hepatocyte nursing cells, tissue engineered to liver- like structures at high density. Treatment started after complete recovery from anesthesia and was performed continuously. A positive influence on peripheral vascular resistance and a reduced need of catecholamine dosage was observed in the treatment group. Hybrid liver support with a cell module upscaled for clinical application significantly prolonged survival time in animals after hepatectomy with the longest survival being 26 hours in the control group an 57 hours in the treatment group.
Abstract: Hybrid liver systems are being developed as temporary extracorporeal liver support therapy. The overview given here emphasizes the development of both hepatocyte culture models for bioreactors and of systems for clinical therapy. In vitro studies demonstrate long term external metabolic function in isolated primary hepatocytes within bioreactors. These systems are capable of supporting essential liver functions. Animal experiments verify the possibility of upscaling bioreactors for clinical treatment. However, since there is no reliable animal model for investigating the treatment of acute liver failure, the promising results obtained from these studies have limited relevance to human beings. The small number of clinical studies performed thus far are not sufficient to enable any conclusions concerning improvements in the therapy of acute liver failure. Although important progress has been made in the development of these systems, multiple hepatocyte culture models and bioreactor constructions are being discussed in the literature, indicating competition in this field of medical research. For the use of hepatocytes and sinusoidal endothelial cells in coculture, a bioreactor has been designed. The construction is based on capillaries for hepatocyte aggregate immobilization. Four separate capillary membrane systems, each permitting a different function, are woven in order to create a three-dimensional network. Cells are perfused via independent capillary membrane compartments. Decentralized oxygen supply and carbon dioxide removal with low gradients is possible. The parallel use of identical units enables easy upscaling. Initial studies on the use of discarded organs that are unsuitable for transplantation as a source for primary human liver cells seem to be promising.
Abstract: The aim of this study was to evaluate the effects of a hybrid liver support system (LSS) on cardiopulmonary function in nine healthy pigs. A hybrid LSS containing primary pig hepatocytes was connected to fully alert animals. The extracorporeal blood flow was maintained between 200-240 ml/min using a roller pump. Continuous plasma flow through the hybrid LSS was 50-60 ml/min. Hemodynamic and pulmonary gas exchange parameters were compared 1 hour before and 1 hour after connection to as well as 1 hour before and 1 hour after disconnection from the hybrid LSS. The hybrid LSS did not influence significantly hemodynamics and pulmonary gas exchange in this group of healthy and awake pigs. It can be concluded that the used LSS did not cause a cardiopulmonary effect per se and should be evaluated further concerning its function as a liver support system in an animal model of acute hepatic failure.
