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Thomas M van Gulik

Publications and source records attributed to Thomas M van Gulik.

At least 19 recordsLinked to original sources

Evidence for Galalpha(1-3)Gal expression on primary porcine hepatocytes: implications for bioartificial liver systems.

BACKGROUND/AIMS: To bridge acute liver failure (ALF) patients to orthotopic liver transplantation, several bioartificial liver (BAL) systems have been developed. The bio-component of most BAL systems consists mainly of porcine hepatocytes. Plasma or blood of ALF patients is perfused through the BAL thereby contacting porcine hepatocytes. Xenogeneic BAL systems may suffer from hyperacute rejection similar to whole-organ xenotransplants. Hyperacute rejection is mediated by antibodies directed against Galalpha(1-3)Gal, a carbohydrate structure present on most mammalian cells. Galalpha(1-3)Gal is produced by the enzyme alpha1,3-galactosyltansferase (alphaGal-T). Conflicting data have been published concerning Galalpha(1-3)Gal expression on hepatocytes in intact porcine liver. We investigated whether isolated porcine hepatocytes express Galalpha(1-3)Gal. METHODS: Immunofluorescence, flow cytometry, RT-PCR and enzyme activity assays were performed on freshly isolated and cultured porcine hepatocytes and liver biopsies. Anti-Galalpha(1-3)Gal antibodies were measured in plasma from patients treated with BAL by ELISA. RESULTS: Isolated porcine hepatocytes express (alphaGal-T) at low levels and Galalpha(1-3)Gal is present in low quantities on these cells, in contrast to hepatocytes in situ. Furthermore, IgG and IgM anti-Galalpha(1-3)Gal are depleted from the plasma of ALF patients during BAL treatment. CONCLUSIONS: Isolation and culture of porcine hepatocytes induce Galalpha(1-3)Gal expression, which may elicit immunological responses potentially compromising BAL functionality.

Animals↗

Improved rat liver preservation by hypothermic continuous machine perfusion using polysol, a new, enriched preservation solution.

For experimental machine perfusion (MP) of the liver, the modified University of Wisconsin solution (UW-G) is most often used. In our search for an enriched MP preservation solution, Polysol was developed. Polysol is enriched with various amino acids, vitamins, and other nutrients for the liver metabolism. The aim of this study was to compare Polysol with UW-G for MP preservation of the liver. Rat livers were preserved during 24 hours with hypothermic MP using UW-G (n = 5) or Polysol (n = 5). Hepatocellular damage (aspartate aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase [LDH], alpha-glutathione-S-transferase [alpha-GST]) and bile production were measured during 60 minutes of reperfusion (37 degrees C) with Krebs-Henseleit buffer. Control livers were reperfused after 24 hours of cold storage in UW (n = 5). MP using UW-G or Polysol showed less liver damage when compared with controls. Livers machine perfused with Polysol showed less enzyme release when compared to UW-G. Bile production was higher after MP using either UW-G or Polysol compared with controls. In conclusion, machine perfusion using Polysol results in better quality liver preservation than cold storage with UW and machine perfusion using UW-G.

Adenosine↗

Dutch surgery in Japan.

An isolation policy was adopted in feudal Japan from 1639 to 1853 owing to the fear of foreign influence. During those 200 years of isolation, all foreigners were withheld from the country with the exception of the Dutch, who were permitted to establish a trading post on a small island in the Bay of Nagasaki, called Decima. Western culture and science reached the Japanese exclusively through the Dutch on Decima. Health care on Decima was provided by Dutch barber-surgeons, who introduced Western surgical practice in Japan. Official interpreters were the only Japanese allowed on Decima. It was from among these interpreters that the first Japanese surgeons arose who, having mastered the Dutch language, translated several Dutch anatomic and surgical texts. Genpaku Sugita translated a Dutch anatomy textbook into Japanese, which was completed in 1774. This book, entitled Kaitai Shinsho [New Book on Anatomy], was the first Western scientific monograph to be translated entirely into Japanese. Several Dutch surgical schools were founded through which Dutch surgery, known in Japan as "surgery of the red-haired" was propagated. According to the custom of the surgical guilds in Holland, certificates were granted to Japanese apprentices who had completed their training in Dutch surgery. About 60 Dutch surgeons had served on Decima up to 1850, providing the basis for surgery to develop in Japan. Among them, Philipp Franz von Siebold was an exceptional scholar who also had a great impact in making Japanese culture known to the Western world.

Anatomy↗

Thrombolytic therapy for acute superior mesenteric artery occlusion.

The aim of this review is to evaluate thrombolytic therapy for acute superior mesenteric artery occlusion as an alternative or adjunctive treatment modality to surgical therapy and to provide current knowledge for timely and informed decisions regarding treatment of acute mesenteric ischemia. A systematic analysis of the available literature from 1966 to 2003 regarding thrombolytic therapy for superior mesenteric artery thromboembolism was performed. A total of 20 case reports and seven small series covered 48 patients with acute superior mesenteric artery thromboembolism. In the herein reviewed series, thrombolytic therapy of acute superior mesenteric artery thromboembolism resulted in angiographic resolution of the thromboembolism in 43 patients, in clinical success without requiring additional surgical intervention in 30 patients, and in survival in 43 patients, with similar complication rates as in thrombolytic treatment of peripheral vascular occlusions. Remission of abdominal pain during the first few hours of treatment formed the most important indicator of therapeutic success. Insufficient evidence from reviewed literature is available to determine the relative effectiveness and safety of thrombolytic treatment for acute superior mesenteric artery thromboembolism; however, initial results appear to be promising. Thrombolytic therapy can be effective relatively quickly, may obviate surgery, and has the potential to resolve the clot completely. In some cases it can be used as an alternative or neo-adjunctive treatment modality to surgery. A treatment guideline for thrombolysis of acute superior mesenteric artery thromboembolism should be developed.

Algorithms↗

Delayed massive hemorrhage after pancreatic and biliary surgery: embolization or surgery?

OBJECTIVE: To analyze the management of delayed massive hemorrhage (DMH) after major pancreatic and biliary surgery. SUMMARY BACKGROUND DATA: Despite a decreased mortality rate for pancreatic and biliary surgery, DMH is still an important cause of postoperative mortality. The aim of the present study was to analyze the management of DMH after pancreatic and biliary surgery, and specifically to assess the role of embolization and surgical intervention. METHODS: The study group (SG) consisted of 1010 patients from 1994 to 2002 who underwent pancreatic or biliary surgery (cholecystectomy excluded). Patients from a previous study (1983-1993, n = 686) were used as a historical control group (HCG). RESULTS: The incidence of DMH (SG 2.3% vs. HCG 3.2%) declined somewhat but did not differ significantly between both periods. The number of patients with a septic complication (SG 74% vs. HCG 50%) and a sentinel bleed (SG 78% vs. HCG 100%) before the onset of DMH did not differ significantly. Embolization (SG 2 of 2 patients vs. HCG 0 of 2 patients) was not used frequently. Successful outcome after surgical intervention (SG 14 of 16 patients vs. HCG 8 of 14 patients) and the surgical procedures performed to obtain hemostasis were comparable and overall mortality (SG 22% vs. HCG 29%) was comparable. CONCLUSIONS: The incidence of DMH declined somewhat from 3.2% to 2.3% over the past years. Most patients present with septic complications and a sentinel bleed before onset of DMH. Despite general acceptance of embolization in our unit, it was used infrequently in patients with DMH. Aggressive surgical intervention was the treatment of choice in patients with DMH after pancreatic or biliary surgery.

Adult↗

Bovine intestinal alkaline phosphatase attenuates the inflammatory response in secondary peritonitis in mice.

Lipopolysaccharide (LPS) contributes importantly to morbidity and mortality in sepsis. Bovine intestinal alkaline phosphatase (BIAP) was demonstrated to detoxify LPS through dephosphorylation. LPS injection combined with BIAP reduced inflammation and improved survival in various experimental settings. In this study, single-dose intravenous administration of BIAP (0.15 IU/g) was applied in a murine cecal ligation and puncture (CLP) model of polymicrobial sepsis. Saline was given as control (S group). Treatment with BIAP prior to CLP (prophylaxis; BIAP-P group) or shortly after (early treatment; BIAP-ET group) reduced cytokine concentrations in plasma and peritoneal lavage fluid (PLF). Tumor necrosis factor-alpha peak levels decreased from 170 pg/ml (S) to 57.5 (BIAP-P) and 82.5 (BIAP-ET) in plasma and in PLF from 57.5 pg/ml (S) to 35.3 (BIAP-P) and 16.8 (BIAP-ET) (all, P < 0.05). Peak interleukin-6 levels in plasma decreased from 19.3 ng/ml (S) to 3.4 (BIAP-P) and 11.5 (BIAP-ET) and in PLF from 32.6 ng/ml (S) to 13.4 (BIAP-P) and 10.9 (BIAP-ET) (all, P < 0.05). Macrophage chemoattractant protein 1 peak levels in plasma decreased from 2.0 ng/ml (S) to 1.0 (BIAP-P) and 0.7 (BIAP-ET) and in PLF from 6.4 (S) to 2.3 (BIAP-P) and 1.3 ng/ml (BIAP-ET) (all, P < 0.05). BIAP-treated groups showed decreased transaminase activity in plasma and decreased myeloperoxidase activity in the lung, indicating reduced associated hepatocellular and pulmonary damage. Survival was not significantly altered by BIAP in this single-dose regimen. In polymicrobial secondary peritonitis, both prophylactic and early BIAP treatment attenuates the inflammatory response both locally and systemically and reduces associated liver and lung damage.

Alanine Transaminase↗

Recurrent disease after microscopically radical (R0) resection of periampullary adenocarcinoma in patients without adjuvant therapy.

The survival rate after microscopically radical resection of pancreatic duct adenocarcinoma is still poor. Patients with ampulla of Vater and distal common bile duct adenocarcinoma indicate a much more favorable prognosis. Controversy exists as to whether adjuvant therapy could improve the outcome in these patients after resection. The aim of the present study was to analyze the pattern of recurrence in patients with periampullary adenocarcinoma after pancreatoduodenectomy. Between January 1992 and December 2002, all patients with an R0 resection were identified and used for this analysis. A total of 190 patients underwent a microscopically radical resection and received no adjuvant therapy. Of those, 72 patients were diagnosed with pancreatic duct adenocarcinoma, 86 patients were diagnosed with ampulla of Vater adenocarcinoma, and 31 patients were diagnosed with distal common bile duct adenocarcinoma. Recurrent disease was indicated in 81% of the patients with pancreatic duct adenocarcinoma, 50% of the patients with ampulla of Vater adenocarcinoma, and in 74% of the patients with bile duct adenocarcinoma. Multivariate analysis revealed that lymph node metastases were prognostic for recurrent disease in patients with pancreatic duct adenocarcinoma (P = 0.038). The depth of invasion (T4, P < 0.032) and lymph node metastases (P < 0.001) were prognostic in patients with ampulla of Vater adenocarcinoma. Poor tumor differentiation (P < 0.001) was prognostic in patients with distal bile duct adenocarcinoma. Selected patients with periampullary malignancies exhibited a high recurrence rate and should be encouraged to enroll in clinical trials for adjuvant treatment including local therapy (radiotherapy) according to the identified prognostic factors.

Ampulla of Vater↗

Inhibition of coagulation and inflammation by activated protein C or antithrombin reduces intestinal ischemia/reperfusion injury in rats.

OBJECTIVE: To examine whether administration of activated protein C or antithrombin reduces local splanchnic derangement of coagulation and inflammation and attenuates intestinal dysfunction and injury following intestinal ischemia/reperfusion. DESIGN: Randomized prospective animal study. SETTING: University research institute. SUBJECTS: Adult male Wistar rats, weighing 300-325 g (n = 72). INTERVENTIONS: Rats were subjected to superior mesenteric artery occlusion consisting of 20 or 40 mins of ischemia and 3 hrs of reperfusion. A randomized intravenous administration of vehicle (0.9% NaCl), heparin, antithrombin, or activated protein C was performed during ischemia, 15 mins before reperfusion. Coagulation and fibrinolysis variables obtained from portal blood were correlated with mucosal fibrin deposition (determined by anti-rat fibrin antibody staining), intestinal function (glucose/water clearance), and intestinal injury (histologic evaluation by Park/Chiu score). MEASUREMENTS AND MAIN RESULTS: Activated protein C- or antithrombin-treated animals demonstrated less ischemia/reperfusion-induced intestinal dysfunction and histologic changes compared with control animals, whereas intravenous administration of heparin only showed less histologic derangement. Activated protein C- or antithrombin-treated animals showed less thrombin generation, fibrin degradation products, and fibrin deposition compared with control animals, as confirmed by histologic examination, whereas heparin administration showed only a limited reduction of portal fibrin degradation product concentrations. Furthermore, activated protein C or antithrombin administration markedly inhibited the inflammatory response, as reflected by reduced interleukin-6 plasma concentrations to baseline values, whereas heparin had no effect. CONCLUSIONS: Administration of activated protein C or antithrombin inhibited local and systemic derangement of coagulation and inflammation following intestinal ischemia/reperfusion, diminished mucosal fibrin deposition, and attenuated ischemia/reperfusion-induced intestinal injury. These observations suggest that activated protein C or antithrombin reduces ischemia/reperfusion-induced intestinal injury, both through their anticoagulant and anti-inflammatory effects.

Animals↗

Clinical application of bioartificial liver support systems.

OBJECTIVE: To review the present status of bioartificial liver (BAL) devices and their obtained clinical results. BACKGROUND: Acute liver failure (ALF) is a disease with a high mortality. Standard therapy at present is liver transplantation. Liver transplantation is hampered by the increasing shortage of organ donors, resulting in high incidence of patients with ALF dying on the transplantation waiting list. Among a variety of liver assist therapies, BAL therapy is marked as the most promising solution to bridge ALF patients to liver transplantation or to liver regeneration, because several BAL systems showed significant survival improvement in animal ALF studies. Until today, clinical application of 11 different BAL systems has been reported. METHODS: A literature review was performed using MEDLINE and additional library searches. Only BAL systems that have been used in a clinical trial were included in this review. RESULTS: Eleven BAL systems found clinical application. Three systems were studied in a controlled trial, showing no significant survival benefits, in part due to the insufficient number of patients included. The other systems were studied in a phase I trial or during treatment of a single patient and all showed to be safe. Most BAL therapies resulted in improvement of clinical and biochemical parameters. CONCLUSIONS: Bioartificial liver therapy for bridging patients with ALF to liver transplantation or liver regeneration is promising. Its clinical value awaits further improvement of BAL devices, replacement of hepatocytes of animal origin by human hepatocytes, and assessment in controlled clinical trials.

Critical Illness↗

Preoperative assessment of liver function: a comparison of 99mTc-Mebrofenin scintigraphy with indocyanine green clearance test.

BACKGROUND/AIMS: The indocyanine green (ICG) clearance test is the most frequently used test for preoperative assessment of liver parenchymal function but has its limitations. The aim of this study was to investigate the correlation between ICG clearance test and the liver uptake of 99-Technetium-labelled (99mTc)-Mebrofenin (99mTc-Mebrofenin) as measured with hepatobiliary scintigraphy. METHODS: Fifty-four patients were diagnosed as hepatocellular carcinoma (n=9), hilar tumours (n=20) and 25 patients with non-parenchymal tumours including colorectal metastasis (n=15) and miscellaneous tumours (n=10). One day prior to operation, hepatobiliary 99mTc-Mebrofenin scintigraphy was performed after intravenous injection of 85 MBq and the 15-min clearance rate of ICG (ICG-C15) was measured. RESULTS: The mean ICG-C15 was 86.86+/-1.19% (SEM). The mean 99mTc-Mebrofenin uptake rate was 12.87+/-0.52%/min. A significant correlation was obtained between 99mTc-Mebrofenin uptake rate by scintigraphy and ICG-C15 (r=0.73, P<0.0001). The mean clearance capacity of the right liver segments (79.83+/-1.63, range 47.75-95.97%) was larger than that of the left segments (20.24+/-1.55, range 6.51-52.51%). CONCLUSION: 99mTc-Mebrofenin uptake rate as assessed by scintigraphy is an efficient method for determining liver function and correlates well with ICG clearance. At the same time, 99mTc-Mebrofenin scintigraphy provides information of segmental functional liver tissue, which is of additional use when planning liver resection.

Adult↗

Factor VIII expression in liver disease.

Liver disease is associated with markedly elevated plasma factor VIII (FVIII) levels, whereas the synthesis of many other coagulation factors and proteins is reduced. In order to define the mechanism of FVIII increase, we have determined the expression levels of FVIII, both at mRNA and protein level, in patients with liver disease who underwent partial liver resection. In addition, the expression of von Willebrand factor (VWF) and low density lipoprotein receptor-related protein (LRP), proteins known for their ability to modulate FVIII plasma levels, were examined. Tissue samples for RNA extraction were obtained from 4 patients with cirrhosis, 9 patients with liver failure without cirrhosis and 6 patients with liver metastasis of a colon or rectum carcinoma (control group). In patients with liver cirrhosis hepatic FVIII and LRP mRNA levels were significantly lower than controls (p < or = 0.010), while VWF mRNA was significantly higher (p < or = 0.050). Immunohistochemical analysis revealed that cellular VWF protein distribution was also increased in cirrhotic livers compared to liver tissue from patients with non-cirrhotic liver disease. In cirrhotic tissue enlarged portal veins appeared to overgrow FVIII producing sinusoidal endothelial cells. Similarly, the number of LRP-producing cells appeared to be lower in cirrhotic tissue than in controls. The plasma concentration of both FVIII and VWF was significantly higher in patients with cirrhosis than control subjects (p = 0.038 and 0.010 respectively). These results demonstrate that elevated plasma FVIII levels in liver cirrhosis are associated with increased hepatic biosynthesis of VWF and decreased expression of LRP, rather than increased FVIII synthesis.

Adult↗

Enhancement of endogenous fibrinolysis does not reduce local fibrin deposition, but modulates inflammation upon intestinal ischemia and reperfusion.

This study investigated the contribution of endogenous suppression of fibrinolysis and increased fibrin deposition to intestinal dysfunction and injury in a rat model of intestinal ischemia/reperfusion (I/R), as fibrinolytic inhibition may lead to thrombotic obstructions that compromise microcirculation and promote intestinal injury. Circulatory fibrinolysis was enhanced by intravenous administration of recombinant tissue plasminogen activator (rt-PA) or by inhibition of PAI-I by administration of MA-33H1F7. Coagulation and fibrinolysis parameters obtained from portal blood were correlated to fibrin deposition (determined by anti-rat fibrin antibody staining), intestinal function (glucose/water clearance) and intestinal injury (histological evaluation by Park/Chiu score). Enhanced circulatory fibrinolytic activity, as evidenced by increased portal plasma plasminogen activator activity, elevated fibrin degradation products and decreased levels of PAI-I, did not reduce mucosal fibrin deposition and microthrombosis in postischemic intestinal tissue. Furthermore, rt-PA or anti-PAI-I antibody administration did not attenuate I/R-induced intestinal injury or dysfunction, as demonstrated by intestinal histopathology scores of 4.8+/-0.2 and 4.7+/-0.3 (control I/R group 4.7+/-0.2) and glucose clearances of 47+/-6 and 46+/-9 micro L/min g (control I/R group 30+/-8 micro L/min. g) after 40 minutes of intestinal ischemia and 3 hours of reperfusion, respectively. However, both interventions resulted in decreased levels of interleukin-6, which may indicate fibrin-induced modulation of inflammation. Attempts to enhance the fibrinolytic activity (either by rt-PA or by anti-PAI-I administration), indicated by increased portal plasma levels of released FDP, failed to decrease mucosal fibrin deposition and to attenuate intestinal I/R injury. Based on our observations and previous reports, the contribution of suppressed endogenous fibrinolysis to microcirculatory fibrin deposition and I/R-injury may be of limited importance.

Animals↗

Preoperative assessment of postoperative remnant liver function using hepatobiliary scintigraphy.

UNLABELLED: Hepatic resection is the therapy of choice for malignant and symptomatic benign hepatobiliary tumors. The concept of remnant liver volume (RLV) has been introduced and can be assessed with CT. However, inhomogeneous liver function distribution and a lack of correlation between morphologic hypertrophy and functional recovery fuelled the enthusiasm for functional imaging. The aim of the present study was to assess liver function reserve (LFR) and remnant liver function (RLF) before and after major liver surgery with hepatobiliary scintigraphy (HBS) and to compare scintigraphic results with volumetric CT data and indocyanine-green (ICG) clearance test results. Furthermore, HBS was used to assess functional recovery of liver function, and results were compared with volumetric data. METHODS: Fifteen patients with a partial liver resection were included. HBS was performed before, 1 d after, and 3 mo after surgery. ICG clearance and CT were performed before and 3 mo after surgery. Liver function determined with HBS was compared with ICG and volumetric data. RESULTS: Liver function determination using HBS was highly reproducible. A strong positive association (r = 0.84) was found between LFR determined with HBS and ICG clearance. Little or no association (r = 0.27) was found between CT volumetric analysis and corresponding ICG clearance. A strong positive association (r = 0.95) was found between the RLF determined preoperatively on HBS and the actually measured value postoperatively. A weak positive association (r = 0.61) was found between functional liver regeneration and liver volume regeneration in the 3 mo after partial liver resection. CONCLUSION: HBS offers a unique combination of functional liver uptake and excretion with the ability to assess the preoperative LFR and to estimate the RLF preoperatively. Determination of the RLF instead of the RLV might clarify some of the discrepancies observed in the literature between RLV and clinical outcome in patients with an inhomogeneous liver function. Finally, liver function regeneration can be monitored using HBS.

Adult↗

Results of postoperative radiotherapy for resectable hilar cholangiocarcinoma.

The aim of this study was to assess the value of radiotherapy, and especially intraluminal brachytherapy, after resection of hilar cholangiocarcinoma by analyzing long-term complications and survival. Between 1983 and 1998, 112 patients underwent resection of a hilar cholangiocarcinoma. Of the 91 patients who survived the postoperative period, 20 patients had no additional radiotherapy, 30 patients had only external radiotherapy (46 +/- 11 Gy), and 41 patients had a combination of external (42 +/- 5 Gy) and intraluminal brachytherapy (10 +/- 2 Gy). Overall, 88% of the patients had late complications, with a significantly higher rate of complications occurring among patients receiving external beam irradiation and brachytherapy. Second to abdominal pain (56%), cholangitis (49%) was the most frequent complication and occurred significantly more often in patients who had received brachytherapy. Retrograde bile leakage after closure of the temporary jejunostomy was a troublesome complication in 24% of patients treated with brachytherapy. Overall median survival after treatment with adjuvant radiotherapy was longer than after resection without additional radiation (24 months versus 8 months, respectively). There was, however, no significant benefit from the use of intraluminal brachytherapy. In conclusion, additional radiotherapy after resection of hilar cholangiocarcinoma significantly improved survival and is recommended by giving external beam irradiation but not intraluminal brachytherapy.

Abdominal Pain↗

Decrease in core liver temperature with 10 degrees C by in situ hypothermic perfusion under total hepatic vascular exclusion reduces liver ischemia and reperfusion injury during partial hepatectomy in pigs.

OBJECTIVE: We attempted to assess liver ischemia/reperfusion injury under a mild decrease in core liver temperature of 10 degrees C by in situ hypothermic perfusion during ischemia. METHODS: Liver ischemia was induced in pigs by total hepatic vascular exclusion with concomitant in situ perfusion with hypothermic (4 degrees C) Ringer-glucose (cold perfused group, core liver temperature maintained at 28 degrees C), with normothermic (38 degrees C) Ringer-glucose (warm perfused group) or without in situ perfusion (control group). RESULTS: In the cold perfused, warm perfused, and control groups, 24-hour survival was 5/5, 0/5, and 3/5, respectively. Hemodynamic parameters in the cold perfused group remained stable, whereas pigs in both other groups required circulatory support. Plasma AST and interleukin-6 levels were lower in the cold perfused group than in both other groups. Hepatocellular function was best preserved in the cold perfused group as indicated by complete recovery of bile production during reperfusion and no loss of indocyanine green clearance capacity. In both other groups, bile production and indocyanine green clearance capacity were reduced significantly. The hyaluronic acid uptake capacity of pigs in the cold perfused group or control group did not differ, indicating preserved sinusoidal endothelial cell function. Histopathologic injury scores during reperfusion were significantly lower in the cold perfused group when compared to both other groups. CONCLUSIONS: A mild decrease in core liver temperature of 10 degrees C by in situ hypothermic liver perfusion during ischemia protects the liver from ischemia/reperfusion injury. This protection appears to be related to cooling of the liver rather than to the washout of blood during perfusion.

Animals↗

MARS treatment in posthepatectomy liver failure.

Posthepatectomy liver failure (PHLF) is a dramatic complication following extensive liver resection or liver resection in a compromised liver, leading to death in 80% of cases. Molecular Adsorbent Recirculating System (MARS) is able to extract water and protein bound toxins out of the blood in liver failure patients. This paper describes the initial experience in the Netherlands using the MARS liver assist device in five patients with PHLF. In all patients, improvement of biochemical parameters was observed during MARS treatment along with clinical improvement in three patients. One patient survived. No clear guidelines for MARS treatment and prognostic factors for outcome after MARS treatment with regard to this patient group are available. In this paper, a MARS treatment regimen for PHLF is suggested based on literature and our own experience.

Aged↗

Effect of in situ hypothermic perfusion on intrahepatic pO2 and reactive oxygen species formation after partial hepatectomy under total hepatic vascular exclusion in pigs.

AIM: This study examined attenuation of ischemia and reperfusion (I/R) induced liver injury during liver resections by hypothermic perfusion of the liver under total hepatic vascular exclusion (THVE). METHOD: Reactive oxygen species (ROS) formation, microcirculatory integrity and endothelial cell damage were investigated. Left hemihepatectomy (LHX) was performed without in situ perfusion (control-LHX, n = 5) or with concomitant in situ perfusion with hypothermic (4 degrees C) Ringer-glucose (cold-LHX, n = 5) or normothermic (38 degrees C) Ringer-glucose (warm-LHX, n = 5). Glutathione (GSH) and malondialdehyde (MDA) concentrations, tissue pO2 levels and hyaluronic acid (HA) uptake capacity were determined. RESULTS: After cold, warm and control-LHX, 24 h survival was 5/5, 0/5 and 3/5, respectively. GSH levels were best preserved after cold-LHX during reperfusion. MDA levels increased in all groups without significant differences between the groups during reperfusion. Tissue pO2 levels increased after cold-LHX whereas after warm-LHX and control-LHX, pO2 levels decreased during reperfusion. HA uptake capacity remained normal after cold-LHX. After warm-LHX and control-LHX, HA uptake capacity decreased after 6 h of reperfusion but recovered after 24 h of reperfusion in the control-LHX group. CONCLUSION: Moderate hypothermic perfusion protects the liver from I/R injury during LHX under THVE. This protective effect depended on maintenance of liver microcirculation rather than a reduction in ROS formation.

Animals↗