[Show abstract][Hide abstract] ABSTRACT: Introduction. Pancreatic injury can manifest after major hepatectomy under vascular control. The main mechanism involved seems to be remote oxidative injury due to "spillage" of reactive oxygen species and cytokines from the liver. The aim of this study is to evaluate the role of desferrioxamine in the prevention of pancreatic injury following major hepatectomy. Methods. Twelve Landrace pigs were subjected to a combination of major hepatectomy (70-75%), using the Pringle maneuver for 150 minutes, after constructing a porta-caval side-to-side anastomosis. The duration of reperfusion was 24 hours. Animals were randomly divided into a control group (n = 6) and a desferrioxamine group (DFX, n = 6). DFX animals were treated with continuous IV infusion of desferrioxamine 100 mg/kg. Pancreatic tissue injury, c-peptide and amylase concentrations, and pancreatic tissue oxidative markers were evaluated. Results. Desferrioxamine-treated animals showed decreased c-peptide levels, decreased acinar cell necrosis, and decreased tissue malondialdehyde levels 24 hours after reperfusion compared with the control group. There was no difference in portal pressure or serum amylase levels between the groups. Conclusions. Desferrioxamine seems to attenuate pancreatic injury after major hepatectomy under vascular control possibly by preventing and reversing production and circulation of oxidative products.
HPB Surgery 06/2012; 2012(2):714672. DOI:10.1155/2012/714672
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the pathophysiology of pancreatitis after major hepatectomy.
The study used ten female pigs. Three served as sham animals (sham group) and were killed after laparotomy to obtain normal tissue samples. Seven animals were subjected to major hepatectomy (70-75%), using the Pringle maneuver for 150 min, after constructing a portacaval side-to-side anastomosis (hepatectomy group). Duration of reperfusion was 24 h.
Pancreatic tissue sampled 24 h after reperfusion had increased necrosis and edema in comparison to sham group and to tissue sampled at 12 h. Tissue malondialdehyde (MDA) did not differ significantly between samples at 12 and 24 h but was increased in the hepatectomy group in comparison to sham animals. Percentage increase in portal MDA content during reperfusion was greater at 12 h of reperfusion in comparison to the increase after 24 h. Portal pressure increased significantly after 12 h of reperfusion. Serum amylase and C-peptide increased during reperfusion in comparison to baseline levels.
The findings suggest that intraoperative portal congestion is not the only cause of the development of pancreatitis after major hepatectomy. The oxidative markers suggest that reactive oxygen species produced during vascular control may be responsible as well.
Surgery Today 11/2011; 42(4):368-75. DOI:10.1007/s00595-011-0039-y · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to develop a porcine model of post-operative liver failure (POLF) that could accurately reproduce all the neurological and metabolic parameters of the corresponding clinical syndrome that may develop after extensive liver resections.
In our model, we induced POLF by combining extended left hepatectomy and ischemia of the small liver remnant of 150 min duration. Subsequently, the remnant liver parenchyma was reperfused and the animals were closely monitored for 24 h.
Twelve Landrace pigs (weight 25-30 kg) were randomly assigned in two groups; eight of them constituted the experimental group, in which POLF was induced (POLF group, n = 8), whereas the rest of them (n = 4) were included in the control group (sham laparotomy without establishment of POLF). RESULTS (MEANS ± SD): All POLF animals gradually developed neurological and biochemical signs of liver failure including, among many other parameters, elevated intracranial pressure (24.00 ± 4.69 versus 10.17 ± 0.75, P = 0.004) and ammonia levels (633.00 ± 252.21 versus 51.50 ± 9.49, P = 0.004) compared with controls. Histopathologic evaluation of the liver at the end of the experiment demonstrated diffuse coagulative necrosis and severe architectural distortion of the hepatic parenchyma in all POLF animals.
Our surgical technique creates a reproducible porcine model of POLF which can be used to study the pathophysiology and possible therapeutic interventions in this serious complication of extensive hepatectomies.
Journal of Surgical Research 07/2011; 170(2):e233-42. DOI:10.1016/j.jss.2011.06.006 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is accumulating clinical evidence that acute liver failure may be regularly associated with myocardial injury. To test this hypothesis in a standardized experimental setting, we used two porcine models of ALF.
In 14 domestic pigs ALF was induced by either a) surgical devascularization of the liver (DV group, n = 7), or b) partial (70-75%) hepatectomy and ischaemia/reperfusion of the liver remnant for 150 min (I/R group, n = 7). Four additional animals constituted the sham operation group. All animals were monitored for a 12-h period, at the end of which their hearts were harvested. Plasma troponin I (cTnI) and malondialdehyde (MDA) were measured before the operation (baseline) and at 6 h and 12 h postoperatively. The harvested hearts were histologically analysed, appointing a score from 0 (no injury) to 3 (maximum injury) to selected injury indicators.
In the sham group, all cTnI measurements and total myocardial injury score were zero in all animals. In both ALF groups, plasma cTnI levels increased by the 6(th) and remained elevated up to the 12(th) postoperative hour (p < 0.01 vs. sham animals). Total myocardial injury score and total histological score revealed some extent of myocardial injury. The rise of MDA levels suggests an underlying oxidative mechanism.
Our study provides direct evidence of early myocardial injury in the setting of acute liver failure in pigs. The mechanism of injury remains to be elucidated.
[Show abstract][Hide abstract] ABSTRACT: This study aims to evaluate whether injury of gut mucosa in a porcine model of post-hepatectomy liver dysfunction can be prevented using antioxidant treatment with desferrioxamine.
Post-hepatectomy liver failure was induced in pigs combining major (70%) liver resection and ischemia/reperfusion injury. An ischemic period of 150 minutes, was followed by reperfusion for 24 h. Animals were randomly divided into a control group (n = 6) and a desferrioxamine group (DFX, n = 6). DFX animals were treated with continuous IV infusion of desferrioxamine 100 mg/kg. Intestinal mucosal injury (IMI), bacterial and endotoxin translocation (BT) were evaluated in all animals. Intestinal mucosa was also evaluated for oxidative markers.
DFX animals had significantly lower IMI score (3.3 ± 1.2 vs. 1.8 ± 0.9, p < 0.05), decreased BT in the portal circulation at 0 and 12 h of reperfusion (p = 0.007 and p = 0.008, respectively), decreased portal endotoxin levels at 6 (p = 0.006) and 24 h (p = 0.004), decreased systemic endotoxin levels (p = 0.01) at 24 h compared to controls. Also, 24 h post-reperfusion mucosal malondialdehyde and protein carbonyls were decreased in DFX animals compared to controls (4.1 ± 1.2 vs. 2.5 ± 1.2, p = 0.05 and 0.5 ± 0.1 vs. 0.4 ± 0.1, p = 0.04 respectively).
Desferrioxamine seems to attenuate mucosal injury from post-hepatectomy liver dysfunction possibly through blockage of iron-catalyzed oxidative reactions.
Journal of Gastrointestinal Surgery 03/2011; 15(5):809-17. DOI:10.1007/s11605-011-1475-0 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Postoperative liver failure remains a major cause of morbidity and mortality after extensive hepatectomies. This study aims to evaluate the effectiveness of a hepatocyte bioreactor in the treatment of experimental post-hepatectomy liver failure. Our experimental model included a combination of a side-to-side portacaval shunt, occlusion of the hepatoduodenal ligament for 150 min, 70% hepatectomy, and reperfusion. Following the development of liver failure, 12 pigs were randomized into a control group (n = 6) and a treatment group (n = 6). Both groups underwent extracorporeal perfusion through a plasma separation device, a membrane oxygenator, and two parallel bioreactors. In the latter group, the bioreactors were loaded with 10 billion fresh hepatocytes, isolated from a donor pig. Following hepatocyte treatment, all animals were maintained for 24 h under mechanical ventilation, with intravenous fluid and glucose supplementation. Hemodynamic parameters, intracranial pressure, and biochemical parameters were measured. Liver biopsies were obtained during the 24-h autopsy. The extracorporeal circuit was well-tolerated hemodynamically. Treated animals had lower intracranial pressure compared with controls (at 24 h, 15 ± 3.1 vs. 22 ± 3.5 mm Hg, P = 0.006). Plasma ammonia in treated animals was lower compared with controls at 12 h (100 ± 29 vs. 244 ± 131 µmol, P = 0.026). Liver histological study showed decreased necrosis and increased regeneration activity in treated animals compared with controls. Treatment through an extracorporeal hepatocyte bioreactor attenuates brain edema and improves histological and functional parameters of the liver remnant of pigs with posthepatectomy liver failure.
[Show abstract][Hide abstract] ABSTRACT: Liver resections are frequently associated with significant ischemia-reperfusion (I-R) injury of the liver remnant. The aim of this study was to investigate whether deferoxamine (DFO) can ameliorate I-R injury during major hepatectomies performed under vascular exclusion of the liver in a porcine model. Twelve female domestic pigs were divided into control (n = 6) and DFO treatment (n = 6) groups and subjected to 150 min. liver ischemia followed by 70% hepatectomy and 24 hours reperfusion. Pigs in the DFO group received a continuous intravenous infusion of 100 mg/kg DFO. Liver remnant injury was evaluated by liver function tests, hepatic histology as well as serum and liver tissue malondialdehyde (MDA) concentrations. Deferoxamine-treated animals had reduced total bilirubin, gamma-glutamyl transferase and ammonia levels as well as hepatocyte necrosis and oxidative injury. In a subsequent randomized clinical trial using DFO for I-R protection during major liver surgery, preliminary results revealed amelioration of hepatocellular damage, oxidative and inflammatory serum markers and apoptotic response in liver remnant biopsies.
[Show abstract][Hide abstract] ABSTRACT: Extensive experimental studies and a few clinical series have shown that ischemic preconditioning (IPC) attenuates oxidative ischemia/reperfusion (I/R) injuries in liver resections performed under inflow vascular control. Selective hepatic vascular exclusion (SHVE) employed during hepatectomies completely deprives the liver of blood flow, as it entails simultaneous clamping of the portal triad and the main hepatic veins. The aim of the present study was to identify whether IPC can also protect hepatocytes during liver resections performed under SHVE.
Patients undergoing major liver resection were randomly assigned to have either only SHVE (control group, n = 43) or SHVE combined with IPC--10 min of ischemia followed by 15 min of reperfusion before SHVE was applied (IPC group, n = 41).
The two groups were comparable with regard to age, liver resection volume, blood loss and transfusions, warm ischemic time, and total operative time. In liver remnant biopsies obtained 60 min post-reperfusion, IPC patients had significantly fewer cells stained positive by TUNEL compared to controls (19% +/- 8% versus 45% +/- 12%; p < 0.05). Also IPC patients had attenuated hepatocyte necrosis, systemic inflammatory response, and oxidative stress as manifested by lower postoperative peak values of aspartate transaminase, interleukin-6, interleukin-8, and malondialdehyde compared to controls. Morbidity was similar for the two groups, as were duration of intensive care unit stay and extent of total hospital stay.
In major hepatectomies performed under SHVE, ischemic preconditioning appears to attenuate apoptotic response of the liver remnant, possibly through alteration of inflammatory and oxidative pathways.
World Journal of Surgery 08/2009; 33(9):1909-15. DOI:10.1007/s00268-009-0117-0 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study was to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF. 14 adult female domestic pigs were subjected to surgical devascularisation of the liver and were randomised to a study group (DFX group, n = 7), which received post-operative intravenous infusion of DFX (14.5 mg x kg(-1) x h(-1) for the first 6 h post-operatively and 2.4 mg x kg(-1) x h(-1) until completion of 24 h), and a control group (n = 7). Post-operative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis. DFX resulted in reduced BALF protein levels and tissue phospholipase (PL)A(2) activity. Plasma malondialdehyde and BALF nitrate and nitrite concentrations were lower, while catalase activity in the lung was higher after DFX treatment. PLA(2), platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocyte necrosis and total lung injury in the DFX-treated animals. DFX reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA(2) and the attenuation of pneumonocyte necrosis could represent beneficial mechanisms by which DFX improves alveolar-capillary membrane permeability and prevents alveolar space collapse.
European Respiratory Journal 06/2009; 33(6):1429-36. DOI:10.1183/09031936.00123108 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A clinicopathologic presentation of 2 unusual cases of metastatic mesenchymal neoplasms in the pancreas.
The first case concerns a 26-year-old man with a history of intracranial mesenchymal chondrosarcoma (since the age of 17), 2 left lung operations, and 3 right thigh operations. Distal pancreatectomy and splenectomy was performed because of suspicious mass in the pancreas. The second case concerns a 66-year-old woman with a history of uterus leiomyosarcoma (10 years ago) with left axillary and right femoral metastases. She underwent distal pancreatectomy and splenectomy because of suspicious mass measuring 4 x 4 cm, in the pancreatic body.
In the first case, the pathological examination revealed a tumor measuring 3.8 x 3.5 cm and histologically compatible with mesenchymal chondrosarcoma, developing in a vessel lumen and invading into the pancreatic parenchyma. In the second case, the pathological examination showed metastatic leiomyosarcoma of high-grade malignancy. The incidence of metastatic pancreatic tumors has been reported to be only 1.6% to 3%. Most of these tumors were of epithelial origin, and the most common sites of the primary lesions were the lung, kidney, and gastrointestinal tract.
The cases of metastatic uterus leiomyosarcoma and the metastatic intracranial chondrosarcoma are, to our knowledge, the first to be described.
[Show abstract][Hide abstract] ABSTRACT: We report the case of a 57-year-old female patient with an ovarian neoplasm of insular carcinoid and mucinous cystadenoma of low malignant potential, arising in a cystic teratoma of the right ovary. Additionally, a mature teratoma of the left ovary was present. This is an extremely rare combination of primary tumors in the ovary. The possible common histogenesis of the afore-mentioned tumors is discussed.
European journal of gynaecological oncology 02/2006; 27(6):636-7. · 0.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the case of a 46-year-old female who underwent a routine operation of herniorraphy for a right inguinal hernia. Physical findings revealed a moveable tender mass in the right lower inguinal area. Pathological examination revealed a mass with multiple nodules scattered in the inguinal hernia sac. The histological features of these nodules were compatible with malignant peritoneal mesothelioma (MPM). The incidental finding of MPM in the inguinal hernia sac is very rare. The incidence of this neoplasm is 2-2.6 cases per million annually, and the prognosis is very poor.
European journal of gynaecological oncology 02/2006; 27(5):534-6. · 0.61 Impact Factor