Video-assisted subtotal or near-total thyroidectomy for Graves' disease.

BACKGROUND: Surgery remains the treatment of choice for patients with Graves' disease. The purpose of the present study was to assess the usefulness and efficacy of video-assisted subtotal or near-total thyroidectomy in patients with Graves' disease. METHODS: Between March 2000 and December 2004, 63 patients with Graves' disease underwent video-assisted subtotal, near-total or total thyroidectomy. Fifty-three patients (84 per cent) were considered for surgery after failure of antithyroid drug and radioiodine therapy, whereas the other ten patients were initially selected for surgical treatment based on their own preference. Treatment outcome was evaluated, including surgical complications, thyroid function, quality of life and patient satisfaction with the surgical result. RESULTS: All patients were operated on using a video-assisted technique, with some modifications depending on time and experience. There were no conversions to open surgery. Three patients (5 per cent) had temporary recurrent laryngeal nerve palsy that recovered spontaneously. Most patients were satisfied with the surgical results, particularly regarding the placement of the surgical scars. CONCLUSION: Video-assisted subtotal or near-total thyroidectomy is a safe and effective procedure for treatment of Graves' disease.

Inhibitory effects of safe and novel SOD derivatives, galactosylated-SOD, on hepatic warm ischemia/reperfusion injury in pigs.

BACKGROUND/AIMS: Oxygen-derived free radicals such as superoxide play an important role in ischemia/reperfusion (IR) injury during and after extensive liver surgery or liver transplantation. Superoxide dismutase (SOD) has protective effects against hepatic IR injury. The effect of native SOD is, however, limited because of rapid elimination from the blood circulation and poor affinity for liver cells. It was reported by our collaborators that a SOD derivative modified with galactose (Gal-SOD) was selectively delivered well to hepatocytes by direct attachment to galactose receptors. In the present study, the efficacy of this agent for attenuating hepatic warm IR injury was investigated using the pig model. METHODOLOGY: After 45-min clamping of the hepatic artery and portal vein, pigs were divided into 3 groups according to the following treatments. Ten milliliters of normal saline in Group 1 (n=5), 10,000 units/kg of native SOD in Group 2 (n=5) and 10,000 units/kg of Gal-SOD in Group 3 (n=5) were given just prior to hepatic reperfusion. Liver function including clearance of total bile acid (TBA) and hyaluronic acid (HA) was investigated. Lipid peroxidase of the liver tissue (LPO) and histological findings were examined. In addition, survival rates of the pigs in each group were evaluated. RESULTS: The survival rates at the 7th day after the operation were 60%, 80%, 100% in Groups 1, 2 and 3, respectively. Liver function tests, clearance of TBA and HA, and LPO levels were significantly improved in Groups 3 over findings in Groups 1 and 2. Congestion of hepatic tissues and vacuolization of hepatocytes in Group 3 were less than those in Groups 1 and 2. These results suggested that oxygen-derived free radicals were scavenged by Gal-SOD and IR injury was attenuated. CONCLUSIONS: A safe and novel agent, Gal-SOD has a protective effect against hepatic warm IR injury.

Influence of serum from rats with fulminant hepatic failure on hepatocytes in a bioartificial liver system.

Fulminant hepatic failure (FHF) is a life-threatening condition marked by many excessively increased unmetabolized toxins and growth factors. Recently developed bioartificial liver (BAL) systems containing hepatocytes can be used to treat patients with FHF However, the behavior of these hepatocytes on exposure to FHF serum in vitro remains unclear. In the present study, we used FHF rat models and the sera from these rats (i.e., FHF serum) contained elevated inflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), HGF, and TGF-beta1. In addition, 1x10(8) hepatocytes were harvested from the livers of inbred rats and incubated with microcarrier beads. Four hours later, the hepatocyte-coated beads were inoculated into a hollow-fiber module (=BAL system). FHF serum or normal control serum circulated for 6 hours through the BAL system. Expressions of mRNA for albumin, GST A1, CYP 1A2, OTC and c-fos were investigated by RT-PCR, and PCNA staining was performed before and after perfusion. The expressions of albumin, GST A1, and CYP 1A2 mRNAs were markedly decreased, whereas those of OTC and c-fos were modestly decreased. PCNA positive cells were low and showed no difference between FHF and normal serum-exposed hepatocytes. In conclusion, the exposure of hepatocytes to hypercytokinemia, including inflammatory cytokines and positive and negative growth factors, caused a loss in liver specific functions. This environment also failed to facilitate hepatocyte regeneration.

Use of the time-signal intensity curve from dynamic magnetic resonance imaging to evaluate remnant pancreatic fibrosis after pancreaticojejunostomy in patients undergoing pancreaticoduodenectomy.

BACKGROUND: This study assessed the value of the time-signal intensity curve (TIC) obtained from dynamic magnetic resonance imaging (MRI) in the evaluation of remnant pancreatic fibrosis after pancreaticojejunostomy in patients undergoing pancreaticoduodenectomy. METHODS: Two modes of pancreaticojejunostomy-duct-to-mucosa anastomosis (DMA; 24 patients) and pancreatojejunoserosal anastomosis (PJSA; 22 patients)-were used in 46 consecutive patients undergoing pancreaticoduodenectomy. All patients underwent dynamic contrast-enhanced MRI of the pancreas before pancreaticoduodenectomy. Retrospective review of the pancreatic magnetic resonance images and histological examination of the pancreas were performed, and the patterns of TICs from dynamic MRI were compared with the degree of pancreatic fibrosis. Dynamic MRI of the residual pancreas was carried out for 1-3 years after pancreaticoduodenectomy in 26 patients (14 DMA, 12 PJSA) who had a histologically verified normal pancreas with no fibrosis at the time of pancreaticoduodenectomy. RESULTS: Evaluation of preoperative dynamic magnetic resonance images showed that a pancreatic TIC with a rapid rise to a peak followed by a rapid decline (type I) was characteristic of a normal pancreas without fibrosis. Pancreatic TICs with a slow rise to a peak followed by a slow decline or a plateau (types II and III) indicated a fibrotic pancreas. Postoperative pancreatic MRI demonstrated that six of 12 patients with a PJSA had a type II TIC, whereas 12 of 14 patients with a DMA had a type I curve (P = 0.046). CONCLUSION: The TIC obtained from dynamic MRI is a reliable indicator of fibrosis in the remnant pancreas after pancreaticoduodenectomy. Use of a DMA was associated with a lower risk of pancreatic fibrosis 1-3 years after surgery than a PJSA.

An intraductal papillary component is associated with prolonged survival after hepatic resection for intrahepatic cholangiocarcinoma.

BACKGROUND: The outcome after surgery for intrahepatic cholangiocarcinoma (ICC) is dismal and data on long-term survival are not available. This study evaluated prognostic indicators and characteristic features of long-term survivors after hepatic resection for ICC. METHODS: Thirty-one patients who had undergone hepatic resection for ICC were studied. Univariate and multivariate survival analyses of clinicopathological data included an intraductal papillary carcinoma component (IDPCC) in the tumour, which was defined as the histological demonstration of cancer cells growing in a papillary fashion into the lumen of the large bile duct. RESULTS: The overall cumulative survival rate after hepatic resection for ICC was 51.2 per cent at 1 year and 24.5 per cent at 5 years, with a mean(s.d.) survival time of 11(4) months. The presence of IDPCC (P = 0.003), curative resection (P = 0.009) and the absence of perineural invasion (P = 0.040) were identified as favourable independent prognostic factors in multivariate analysis. Eight patients with IDPCC had a 5-year survival rate of 87.5 per cent and a mean(s.d.) survival time of 69(13) months. All seven patients who survived for more than 5 years after surgery had IDPCC, regardless of the gross appearance of the tumour. CONCLUSION: An IDPCC in the tumour resulted in long-term survival after hepatic resection for ICC.

Increased angiogenic growth factor in cyanotic congenital heart disease.

To examine the relationship between the plasma levels of angiogenic growth factors and the severity of cyanosis, 80 patients with cyanotic heart disease (CHD) and 81 healthy controls were studied. Median age and mean arterial blood oxygen saturation respectively were 4.2 years and 81% in CHD subjects and 4.8 years and 98% in controls. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were measured in plasma using enzyme-linked immunoassay. Plasma VEGF levels in controls depended negatively on age (p < 0.0001) until 3 months, when VEGF was no longer elevated. No such age dependence was found for HGF. Although VEGF levels did not differ between CHD and control subjects up to the age of 3 months, VEGF was significantly elevated in CHD patients older than 3 months compared to controls of similar age (149 +/- 106 vs 65 +/- 23 pg/ml, p < 0.0001). Moreover, the VEGF levels were negatively correlated with oxygen saturation (p = 0.03) and positively correlated with hemoglobin (p = 0.004) in CHD patients aged between 3 months and 10 years. Although the physiologic elevation of VEGF in the neonatal period decreases rapidly if oxygen saturation is normal, VEGF elevations persist if systemic hypoxia is present.

Soluble forms of the selectin family in children with Kawasaki disease: prediction for coronary artery lesions.

AIM: To investigate the relationship between the plasma levels of soluble forms of the selectin family and the incidence of coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: Thirty-three patients with KD, including group A patients (n = 22) who had no CALs and group B patients (n = 11) who had CALs, as well as age-matched febrile (n = 10) and afebrile controls (n = 11), were studied. RESULTS: Peak plasma E-selectin levels (172.0 +/- 58.6 ng ml(-1)) occurred during the acute phase of KD, while peak plasma P-selectin levels (260.3 +/- 43.2 ng ml(-1)) occurred during the subacute phase of the illness (p<0.05). Plasma L-selectin levels (1757.3 +/- 244.3 ng ml(-1)) during the convalescent phase tended to be higher than in either the acute or the subacute phase (not significant). Before intravenous immunoglobulin treatment, the plasma levels of E- (225.1 +/- 46.8 ng ml(-1)) and P-selectin (259.4 +/- 76.2 ng ml(-1)) of patients with CALs (n = 11) were significantly higher than those of patients (n = 22) with no CALs (E-selectin, 131.6 +/- 36.9 ng ml(-1); P-selectin, 184.9 +/- 84.6 ng ml(-1); p < 0.05). When a plasma E-selectin value before immunoglobulin treatment of >184.7 ng ml(-1) was used as the cut-off point, the sensitivity and specificity for the incidence of CALs were 81.8% and 90.9%, respectively. These findings demonstrate the relationship between plasma levels of selectins and disease severity of Kawasaki vasculitis. CONCLUSION: Higher plasma levels of E-selectin may have potential as a predictor of the incidence of coronary artery lesions in Kawasaki disease patients.

Assessment of the ability of myocardial contrast echocardiography with harmonic power Doppler imaging to identify perfusion abnormalities in patients with Kawasaki disease at rest and during dipyridamole stress.

The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg x kg(-1)) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (kappa = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (kappa = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (kappa = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

Identification of extracapsular invasion of the metastatic lymph nodes as a useful prognostic sign in patients with resectable colorectal cancer.

PURPOSE: The present study was undertaken to evaluate whether the microscopic patterns of distribution and extracapsular invasion of cancer cells in the regional lymph nodes were linked to the survival rates for patients with advanced colorectal cancer who undergo a curative surgical resection. METHODS: Two hundred ninety-six surgically resected metastatic lymph nodes from 84 patients with node-positive colorectal cancer were microscopically examined. The distribution of cancer cells in the lymph nodes were grouped into two types: type A (> or =50 percent cancer) and type B (<50 percent cancer). The extracapsular invasion of cancer cells in the nodes were divided into three subgroups: pattern X (no evidence of cancer cell invasion into the adjacent tissue); pattern Y (less than five cancer cells were seen in the adjacent tissue); and pattern Z (more than five cancer cells invaded the adjacent tissue). The patients, based on these microscopic manifestations of metastatic patterns in the nodes, were divided into three groups: Group 1, patients with pattern X nodal metastases only; Group 2, patients with pattern Y and pattern (X + Y) nodal metastases; and Group 3, patients with pattern Z, pattern (X + Z), pattern (Y + Z), and pattern (X + Y + Z) nodal metastases. RESULTS: The survival rates and disease-free survival rates for patients with metastatic lymph nodes showing an extracapsular invasion pattern (Groups 2 and 3) were significantly worse than those for patients with metastatic nodes showing no extracapsular invasion pattern only (Group 1; P < 0.01). There was no significant difference for the above-cited survival rates among the groups classified according to the Dukes and TNM systems. CONCLUSIONS: It is the thesis of this article that the identification of extracapsular invasion of the metastatic lymph nodes can be taken as a useful prognostic sign in patients with resectable colorectal cancer.

Human colon cancer produces a factor which induces the proliferation of venous endothelial cells.

This study was performed to investigate whether colorectal cancers produce proliferative factors for venous endothelial cells, and whether the proliferative activity is related to basic FGF and VEGF and also to the clinicopathological findings. Surgically resected specimens of 17 colorectal cancer patients were fragmented and cultured, and the supernatant was collected. A human umbilical endothelial cell line (EA-hy 926 cells) was incubated with the supernatant. The proliferative activity was examined and the levels of basic FGF and VEGF were measured. The activities were found to be significantly related to VEGF, the depth of tumor invasion and the tumor stage.

Soluble forms of P-, E- and L-selectin in children with Kawasaki disease.

Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis syndrome of unknown origin, that mainly affects small and medium-sized arteries, particularly the coronary artery, which affects primarily infants and young children. Cell adhesion molecules play important roles in the inflammatory process. The aims of this study were to investigate the pathophysiological role of cell adhesion molecules in KD, and to look for the evidence of direct relationship between the plasma levels of soluble cell adhesion molecules and the incidence of coronary artery lesion (CAL). The 52 patients with KD, Group A patients who were clinical responders of initial intravenous immunoglobulin (IVIG) treatment (n = 30), Group B patients who did not respond to the initial IVIG treatment (n = 22), were studied. The circulating E-selectin (105.6 +/- 12.6 ng/ml) in the acute phase of KD, while the peak plasma P-selectin level (238.4 +/- 26.8 ng/ml) occurred in the subacute phase of illness (p < 0.05, respectively). Plasma L-selectin levels (1557.3 +/- 44.3 ng/ml) during the convalescent phase tend to higher than in the acute and in the convalescent phases (p = NS). The analysis of paired samples in Group A patients before (E-selectin: 131.2 +/- 9.8 ng/ml, P-selectin: 216.6 +/- 13.4 ng/ml) and 48 hour after (E-selectin: 98.9 +/- 9.2 ng/ml, P-selectin: 153.9 +/- 34.1 ng/ml) IVIG administration revealed significantly lower values of E- and P-selectins, however, no significant differences in those in Group B patients. There were also no significant differences in the values of L-selectins between the 2 groups. Before IVIG treatment, the plasma levels of E- (225.1 +/- 46.1 ng/ml) and P-selectin (259.4 +/- 76.2 ng/ml) of patients with CAL (n = 11) were significantly higher than those of patients (n = 41) without CAL (p < 0.05, respectively). Plasma L-selectin levels (1596.9 +/- 385.0 ng/ml) in patients with CAL tended to be lower than those in patients without CAL (p = NS). E- and P-selectin may have potential as predictors of CAL in patients with KD.

A second primary esophageal cancer developing 7 years after chemoradiotherapy for advanced esophageal cancer.

We report a rare case of advanced carcinoma and a second primary carcinoma of the esophagus, both of which were successfully cured by chemotherapy and operation at different times. In 1991, a 38-year-old Japanese man was diagnosed with advanced esophageal cancer, which was unresectable because of the bronchial invasion of the tumor. He was given chemotherapy with cisplatin (CDDP), combined with radiotherapy. During a 4-year follow-up, neither regrowth of the primary tumor nor distant metastasis occurred. In 1995, esophagoscopy demonstrated a lugol-unstained region located 3 cm distal from the area of radiation to the primary lesion shown by esophagography. Histological examination of a biopsy specimen showed the mucosa to be normal. Nevertheless, yearly surveillance by endoscopy and histological examinations showed that the mucosa of the esophagus gradually began to demonstrate mild dysplasia, followed by severe dysplasia; in 1998, a diagnosis of squamous cell carcinoma was made. Esophagectomy with lymph node dissection was performed. Microscopic examination revealed that there had been pathologic complete response for the original advanced esophageal cancer.

Role of carcinoembryonic antigen in the progression of colon cancer cells that express carbohydrate antigen.

Carcinoembryonic antigen (CEA) has been reported to promote the metastatic potential in some experimental tumors. Adhesion molecules are known to play an important role in the process of metastasis. Cytokines, including interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), which are produced by Kupffer cells, induce endothelial cells to express adhesion molecules. As a result, the present study was designed to investigate whether the interaction between CEA and Kupffer cells accelerated the metastatic potential of tumors in the liver. Kupffer cells isolated from the liver of male BALB/c mice were cultured with CEA, either with or without the addition of a cytokine inhibitor. The levels of IL-1beta and TNF-alpha were examined in a culture medium. An adhesion assay of colon cancer cell lines to human umbilical vein endothelial cells was also performed. When CEA was added to the Kupffer cell culture medium, cytokines were produced. Elevated levels of cytokines appeared to lead to increased rates of adhesion of cancer cells to endothelial cells. However, these phenomena were blocked by the addition of cytokine inhibitors. CEA stimulated Kupffer cells to produce cytokines. An elevated number of cytokines have been proven to promote the expression of adhesion molecules in endothelial cells. These processes are therefore considered to contribute to the metastasis of malignant cells to the liver. These results suggest that cytokine inhibitors may therefore play an important role in the inhibition of hepatic metastasis.

Torn-off balloon tip of Z-5 atrial septostomy catheter.

Creation of atrial communication was performed in a newborn with critical aortic stenosis. After the success of the initial creation, balloon atrial septostomy using Z-5 catheter was performed. When catheter was pulled back, the tip of the balloon was torn off. This experience could be considered as noteworthy when using this catheter in patients with unusually thick atrial septum.

Quantitative assessment of severity of ventricular septal defect by three-dimensional reconstruction of color Doppler-imaged vena contracta and flow convergence region.

BACKGROUND: The aim of the present study was to investigate the feasibility and potential value of the computer-controlled, 3D, echocardiographic reconstruction of the color Doppler-imaged vena contracta (CDVC) and the flow convergence (FC) region as a means of accurately and quantitatively estimating the severity of a ventricular septal defect (VSD). METHODS AND RESULTS: We performed a 3D reconstruction of the CDVC and the FC region in 19 patients with an isolated VSD using an ultrasound system interfaced with a Tomtec computer. The variable asymmetric geometry of the CDVC and the FC region could be 3D-visualized in all patients. The 3D-measured areas of CDVC correlated well with volumetric measurements of the severity of VSD (r=0.97, P:<0.001). Regression analysis between the shunt flow rate (calculated from the product of the area of CDVC and the continuous Doppler-derived velocity time integral) and the corresponding reference results (calculated by cardiac catheterization) demonstrated a close correlation (r=0.95, P:<0.001). There was also a good correlation between shunt flow rates calculated using the conventional 2D, 1-axis measurement of the FC isovelocity surface area with the hemispheric assumption (r=0.95, P:<0.001); shunt flow rates calculated using 3D, 3-axis measurements of the FC region (r=0.97, P:<0.01); and reference results by cardiac catheterization. However, the 2D method substantially underestimated the actual shunt flow rate. CONCLUSIONS: The 3D reconstruction of the CDVC and the FC region may aid in quantifying the severity of VSD.

Video-assisted total thyroidectomy.

During the last few years, video-assisted neck surgery (VANS) became one option for thyroid and parathyroid surgery. Reports on VANS were limited to partial resection of the thyroid gland. In this study, we described total thyroidectomy in a patient with Graves' disease. The patient had a thyrotoxic periodic paralysis and methimazole-induced hepatic toxicity as well as hepatitis B virus. Two incisions of 3.5 and 3 cm were placed in the right and left subclavicular regions, respectively. A third incision of 0.5 cm was made just to the right of the midline for the camera. Devascularization of the thyroid gland was performed by using ultrasonically activated shear. Tubal drains were inserted on both sides. The patient suffered from temporary postoperative hoarseness with the voice but had a normal calcium level. The drains were removed on the first postoperative day. The use of VANS may provide a new method for total thyroidectomy with a better cosmetic outcome.

The effect of fenestration procedure on liver regeneration in a case of polycystic liver disease.

We encountered a case of polycystic liver disease for which unroofing and fenestration procedures were performed. The patient was a 55-year-old Japanese female with epigastralgia and abdominal fullness. On computed tomography, millions of low-density areas were seen, particularly in S6, 7, where huge cysts 15 cm in diameter were observed. Magnetic resonance imaging showed a T1 low T2 high-intensity lesion, which was compatible with simple cysts. Unroofing for the cysts in S6, 7 and fenestration of other cysts were performed. Histological examination revealed cuboidal and flat monolayer epithelia with no dysplasia in the wall of the cysts. The postoperative course was uneventful, and the patient's abdominal symptoms remarkably improved. The percentage of the liver volume which was increased in relation to standard liver volume was reduced from 241% (3386 mL: liver parenchyma 750 mL, cysts 2636 mL) to 180% (2525 mL, 1566 mL, 959 mL, respectively) after surgery. The potent mitogen, hepatocyte growth factor, was rapidly increased after the operation and stayed high during the observation period. In this patient, since no liver resection was performed, liver regenerative stimulus was considered to be the loss of space. This phenomenon represents a model of liver regeneration in response to loss of occupied space in an absence of shear stress.

Safe and efficient gene transfer into porcine hepatocytes using Sendai virus-cationic liposomes for bioartificial liver support.

Establishment of a bioartificial liver support system using genetically modified hepatocytes is a potential approach to improve the treatment of severe liver failure. We describe the development of an efficient ex vivo method of gene transfer into a large number of porcine hepatocytes using hemagglutinating virus of Japan (HVJ)-liposome. The transfection efficiency of HVJ-liposome into isolated porcine hepatocytes attached to microcarrier beads was evaluated by beta-galactosidase (beta-gal) staining, fluorescence activated cell sorting analysis for beta-gal and luciferase assay, respectively. To examine the function and cellular damage of transduced hepatocytes, we used enzyme-linked immunosorbent assay for porcine albumin synthesis, lidocaine clearance test (P-450 activity), aspartate aminotransferase, and lactic dehydrogenase release assays. The optimal conditions for gene transfer into the beads-attached hepatocytes using HVJ-liposome included 4 microg of deoxyribonucleic acid with 200 microg of lipid/2 x 105 cells and exposure duration of 90 min. Under these conditions, beta-gal and luciferase genes were transduced to 2.5 x 108 isolated porcine hepatocytes following attachment to the beads. Positive beta-gal staining was observed in more than 30% of the beads-attached hepatocytes. The gene transfer activity of HVJ-liposome method determined by luciferase activities was about 100-fold of that of the lipofection method. Transfected porcine hepatocytes remained functional without any significant cell damage. Our results demonstrated that HVJ-liposome mediated gene transfer into microcarrier-attached porcine hepatocytes is an efficient and nontoxic method suitable for a bioartificial liver support sytem.