Georgios Glantzounis | University of Ioannina (original) (raw)

Papers by Georgios Glantzounis

Antioxidants

Hepatocellular carcinoma (HCC) represents a worryingly increasing cause of malignancy-related mor... more Hepatocellular carcinoma (HCC) represents a worryingly increasing cause of malignancy-related mortality, while Metabolic Associated Fatty Liver Disease (MAFLD) is going to become its most common cause in the next decade. Understanding the complex underlying pathophysiology of MAFLD-related HCC can provide opportunities for successful targeted therapies. Of particular interest in this sequela of hepatopathology is cellular senescence, a complex process characterised by cellular cycle arrest initiated by a variety of endogenous and exogenous cell stressors. A key biological process in establishing and maintaining senescence is oxidative stress, which is present in multiple cellular compartments of steatotic hepatocytes. Oxidative stress-induced cellular senescence can change hepatocyte function and metabolism, and alter, in a paracrine manner, the hepatic microenvironment, enabling disease progression from simple steatosis to inflammation and fibrosis, as well as HCC. The duration of ...

Cancers

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third ... more Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of death worldwide. The management of HCC is complex, with surgical treatment providing long-term survival in eligible patients. This study aims to present the experience of aggressive surgical management of HCC in Greece. Methods: This is a retrospective multicentre clinical study with 242 patients. Results: Most patients were male (79%) and had a median age of 71 yrs. According to the most recent BCLC criteria, 172 patients (71.1%) were classified as BCLC 0-A stage, 33 patients (13.6%) were classified as BCLC B, and 37 (15.3%) were classified as BCLC C. A total of 54% of the patients underwent major hepatectomy. Major postoperative morbidity was 15.6%, and the 90-day postoperative mortality rate was 4.5%. The median follow-up was 33.5 months. Three- and five-year overall survival was 65% and 48%, respectively. The median overall survival was 55 months. Significantly, five...

Free Radical Biology and Medicine

Thrombosis and Haemostasis

Hepatectomy-induced coagulation disturbances have been well studied over the past decade. Cumulat... more Hepatectomy-induced coagulation disturbances have been well studied over the past decade. Cumulative evidence supports the superiority of global coagulation analysis compared with conventional coagulation tests (i.e., prothrombin time or activated partial thromboplastin time) for clinical decision making. Cancer, however, represents an acquired prothrombotic state and liver resection for cancer deserves a more thorough investigation. This prospective observational study was conducted to assess the perioperative coagulation status of patients undergoing major hepatectomies for primary or metastatic hepatic malignancy. Patients were followed up to the 10th post-operative day by serial measurements of conventional coagulation tests, plasma levels of coagulation factors, and thrombin generation assay parameters. An abnormal coagulation profile was detected at presentation and included elevated FVIII levels, decreased levels of antithrombin, and lag time prolongation in thrombin generati...

Journal of Investigative Surgery, 2021

Abstract Purpose Cellular RNA is less compact than DNA, more easily accessible to ROS and therefo... more Abstract Purpose Cellular RNA is less compact than DNA, more easily accessible to ROS and therefore could be more susceptible to oxidative damage. This study was conceived in order to analyze the RNA oxidative damage in the urine of patients undergoing operation for colorectal cancer (CRC), to compare with healthy controls, and correlate with the stage. Materials and methods The study population was constituted by a group of 147 patients and a group of 128 healthy controls. Urine and blood samples were collected before the colonoscopy in all participants and 24 hours post-operatively for those who underwent surgery. Urine 8-hydroxyguanine (8-OHG) was determined as marker of RNA oxidation, and serum uric acid (UA) as antioxidant marker. Results Preoperatively, 8-OHG (ng/ml) values of CRC patients were found to be significantly higher than those of controls (p = 0.001). More specifically, stages II/III had significantly higher 8-OHG values (p < 0.001 and p = 0.007) than stages 0/I. Post-operatively, 8-OHG values were similar to controls (p = 0.053). Preoperatively, UA values (mg/dl) were significantly lower (p = 0.001), while postoperatively were similar to controls (p = 0.069). Conclusion Oxidative RNA damage occurs in CRC patients. Stages II/III are associated with higher values of 8-OHG than stages 0/I. 8-OHG could act as a marker for the identification of patients with advanced disease.

Liver ischaemia-reperfusion (I/R) injury occurs in a number of clinical settings, including liver... more Liver ischaemia-reperfusion (I/R) injury occurs in a number of clinical settings, including liver surgery, transplantation and haemorrhagic shock with subsequent fluid resuscitation. It is well recognised as a significant cause of morbidity and mortality and characterised by oxidative stress accompanied with depletion of antioxidants. Its pathophysiology is complex. This thesis investigates the effect of lobar liver I/R injury on liver microcirculation, hepatic oxygenation, cellular energetics and nitric oxide (NO) metabolism. It evaluates also the hypothesis that the antioxidant N-acetylcysteine (NAC) ameliorates liver I/R injury. Initially an experimental rabbit model was established where both phases (early and late) of liver I/R injury could be studied. New Zealand white rabbits underwent 60 min of lobar ischaemia followed by 7 h of reperfusion. It was found that cannulation of the femoral artery, for monitoring of the arterial blood pressure, induced remote liver injury, which ...

Journal of Clinical Medicine

This study aims to assess the role of Color Duplex Ultrasound with or without contrast media for ... more This study aims to assess the role of Color Duplex Ultrasound with or without contrast media for surveillance following endovascular aortic aneurysm repair (EVAR). A systematic search of the literature published until April 2022 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The pooled rates of endoleak detection through Contrast-Enhanced or Color Duplex Ultrasound (CEUS or CDUS) and Computed Tomography Angiography (CTA) with 95% confidence intervals (CIs) were estimated using random-effect analysis. Thirty-eight studies were considered eligible for inclusion. The total number of patients in the included studies was 5214 between 1997 and 2021. The overall pooled rate of endoleak detection using CDUS and CTA was 82.59% and 97.22%, while the rates for CEUS and CTA were 96.67% and 92.82%, respectively. The findings of the present study support the use of the CEUS for endoleak detection. However, it should be integr...

Cancers, 2022

Hepatocarcinogenesis is a long process with a complex pathophysiology. The current therapeutic op... more Hepatocarcinogenesis is a long process with a complex pathophysiology. The current therapeutic options for HCC management, during the advanced stage, provide short-term survival ranging from 10–14 months. Autophagy acts as a double-edged sword during this process. Recently, two main autophagic pathways have emerged to play critical roles during hepatic oncogenesis, macroautophagy and chaperone-mediated autophagy. Mounting evidence suggests that upregulation of macroautophagy plays a crucial role during the early stages of carcinogenesis as a tumor suppressor mechanism; however, it has been also implicated in later stages promoting survival of cancer cells. Nonetheless, chaperone-mediated autophagy has been elucidated as a tumor-promoting mechanism contributing to cancer cell survival. Moreover, the autophagy pathway seems to have a complex role during the metastatic stage, while induction of autophagy has been implicated as a potential mechanism of chemoresistance of HCC cells. The ...

In Vivo, 2021

Aim: Description of an anesthetic recovery model with endotracheal intubation in rabbits which pr... more Aim: Description of an anesthetic recovery model with endotracheal intubation in rabbits which provides metabolic stability for the study of the late phase of liver ischemia/reperfusion (I/R) injury. Materials and Methods: Two groups of New Zealand rabbits, n=7 in each, were used: Ischemia/reperfusion (I/R) group (45 min of partial liver ischemia/reperfusion) and no intervention (sham) group. Blood alanine aminotransferase, lactate, pH values, mean arterial pressure and pCO 2 were calculated at baseline, and at 2 and 24 h post reperfusion. Tissue samples from left (ischemic) and right (non-ischemic) liver lobes were examined at 2 and 24 h after reperfusion. Results: The I/R group presented significantly higher levels of alanine aminotransferase (p=0.001) at 2 and 24 h, and of lactate (p=0.016) at 2 h post reperfusion. No differences were documented for pH, mean arterial pressure and pCO 2. Histological exanimation revealed significant injury at 24 h post reperfusion for the I/R group. Conclusion: This anesthetic recovery model permitted avoidance of hypoxia and respiratory acidosis, allowing the study of the late phase of I/R injury.

HPB, 2021

Introduction and importance: Intraductal papillary neoplasm of the bile duct (IPNB) is a tumour w... more Introduction and importance: Intraductal papillary neoplasm of the bile duct (IPNB) is a tumour with a very low incidence in the Western world, characterised by a high risk of malignant transformation and unknown prognosis. It is a new entity which was adopted by the WHO in 2010 as a precursor lesion of cholangiocarcinoma. Intrahepatic bile duct is the most common site of origin for IPNB. Case presentation: Hereby, we present a case of an asymptomatic 63-year-old man, referred to our department after routine ultrasonography showing a multifocal cystic lesion on the left hepatic lobe. Further screening modalities (CT, MRI abdo) confirmed a complex cystic liver lesion with atypical features. The patient underwent left hepatectomy. Histopathology showed a cystic type intrahepatic IPNB, which was completely resected (R0). The follow up in 2 yrs post-operation showed no signs of recurrence. Clinical discussion: The diagnosis and management of IPNB remain challenging. A multimodality imaging approach is essential in order to diagnose IPNB, assess tumour location and extent and plan the optimal treatment strategy. Conclusion: Complete surgical resection (R0) with close postoperative follow-up offers long-term survival.

Hellenic Journal of Surgery, 2013

days perform a limited (D1) lymphadenectomy for gastric cancer [6-10]. The Japanese Research Soci... more days perform a limited (D1) lymphadenectomy for gastric cancer [6-10]. The Japanese Research Society for Gastric Cancer (JRSGC) proposed that the lymphatic drainage of the stomach is divided into 16 separate "stations" [11]. The lymph nodes along the lesser curvature of the stomach are classified as stations 1, 3, and 5, and those along the greater gastric curvature as stations 2, 4, and 6. Stations 1,

The American Journal of Surgery, 2010

BACKGROUND: Mild to moderate steatotic livers are used as marginal donors in liver transplantatio... more BACKGROUND: Mild to moderate steatotic livers are used as marginal donors in liver transplantation. Very little is known about the mechanisms of ischemia reperfusion (IR) injury (IRI) in fatty liver. This study aimed to establish whether cytochrome oxidase C (COX) activity is compromised by IRI in fatty liver and whether ischemic preconditioning (IPC) can protect COX activity. METHODS: New Zealand rabbits were fed on a high-cholesterol diet for 8 weeks to induce moderate hepatic steatosis. Three groups were tested. The IR group underwent 60 minutes of ischemia, followed by 7 hours of reperfusion. The IPC group (IPC ϩ IR) underwent 5 minutes of ischemia, followed by 10 minutes of reperfusion and then 60 minutes of ischemia and 7 hours of reperfusion. The control group (sham) underwent the same surgical procedure, but ischemia was not induced. Deoxyhemoglobin, oxyhemoglobin, and change in the redox state of COX was continuously monitored in vivo by near-infrared spectroscopy. COX and citrate synthase (CS) activity assays were carried out on liver biopsy specimens in vitro. Bile was collected continuously during the procedure and analyzed using proton nuclear magnetic resonance spectroscopy. RESULTS: The IR group had decreased COX activity and tissue oxygenation represented by deoxyhemoglobin, oxyhemoglobin, COX, and elevated redox ratios of lactate/pyruvate and ␤-hydroxybutarate/ acetoacetate in vivo and a decrease in COX and CS activity in vitro. The IPC ϩ IR group showed higher levels of all measured parameters in vivo and showed a smaller decrease in COX and CS activity in vitro. CONCLUSION: This study shows that IRI affects COX activity in fatty livers. This is attenuated by IPC.

Journal of Hepatology, 2002

Journal of Gastroenterology and Hepatology, 2010

Background and Aim: Experimental studies have shown protective effect by the nonessential amino a... more Background and Aim: Experimental studies have shown protective effect by the nonessential amino acid glycine to liver ischemia-reperfusion (I/R) injury but the mechanism of action is unknown. Methods: A rabbit model of hepatic lobar I/R was used. Three groups of animals (n = 6) were studied: Sham group (laparotomy alone), ischemia reperfusion (I/R) group (1 h of liver lobar ischemia and 6 h of reperfusion), and a glycine I/R group (intravenous glycine 5 mg/kg prior to the I/R protocol). Systemic and hepatic hemodynamics, degree of liver injury (bile flow, transaminases), hepatic microcirculation, mitochondrial activity (redox state of cytochrome oxidase), bile composition and cytokines (tumor necrosis factor-a and interleukin-8) were measured during the experiment. Results: Glycine administration increased portal blood flow, bile production, hepatic microcirculation and maintained cytochrome oxidase activity as compared with the I/R group during reperfusion. Glycine also reduced bile lactate surge and stimulated acetoacetate release in bile during reperfusion versus the I/R group. Cytokine levels (tumor necrosis factor-a, interleukin-8) and hepatocellular injury (aspartate aminotransferase and alanine aminotransferase) were significantly reduced by glycine administration. Conclusion: Intravenous glycine administration reduces liver warm I/R injury by reducing the systemic inflammatory response, and maintaining cellular energy production.

Future Oncology, 2014

Aim: BMI and the lymph node (LN) ratio can affect short- and long-term outcomes of patients with ... more Aim: BMI and the lymph node (LN) ratio can affect short- and long-term outcomes of patients with gastric cancer. Patients & methods: This study includes 104 consecutive patients with gastric adenocarcinoma who underwent curative gastrectomy divided in two groups: overweight group (group A) and normal weight group (group B). Results: We found that 53.4% of our patients were overweight (group A). The overall rate of postoperative complications was 16.3%, while mortality was 1%. Statistical analyses revealed that postoperative morbidity was significantly higher in group A (p < 0.05). Long-term survival was significantly higher in group B. Cox regression showed a statistically significant correlation between higher BMI and poor long-term survival after curative gastrectomy. Multivariate analysis has identified age and the LN ratios as independent prognostic factors of survival. Conclusion: In this retrospective analysis, BMI and LN ratio were independently associated with survival in...

Current Pharmaceutical Design, 2005

Uric acid is the final product of purine metabolism in humans. The final two reactions of its pro... more Uric acid is the final product of purine metabolism in humans. The final two reactions of its production catalyzing the conversion of hypoxanthine to xanthine and the latter to uric acid are catalysed by the enzyme xanthine oxidoreductase, which may attain two inter-convertible forms, namely xanthine dehydrogenase or xanthine oxidase. The latter uses molecular oxygen as electron acceptor and generates superoxide anion and other reactive oxygen products. The role of uric acid in conditions associated with oxidative stress is not entirely clear. Evidence mainly based on epidemiological studies suggests that increased serum levels of uric acid are a risk factor for cardiovascular disease where oxidative stress plays an important pathophysiological role. Also, allopurinol, a xanthine oxidoreductase inhibitor that lowers serum levels of uric acid exerts protective effects in situations associated with oxidative stress (e.g. ischaemiareperfusion injury, cardiovascular disease). However, there is increasing experimental and clinical evidence showing that uric acid has an important role in vivo as an antioxidant. This review presents the current evidence regarding the antioxidant role of uric acid and suggests that it has an important role as an oxidative stress marker and a potential therapeutic role as an antioxidant. Further well designed clinical studies are needed to clarify the potential use of uric acid (or uric acid precursors) in diseases associated with oxidative stress.

Clinical Science, 2005

Steatotic livers are highly susceptible to I/R (ischaemia/reperfusion) injury and, therefore, the... more Steatotic livers are highly susceptible to I/R (ischaemia/reperfusion) injury and, therefore, the aim of the present study was to evaluate the in vivo effect of NAC (N-acetylcysteine) on hepatic function in the early and initial late phase of warm liver I/R injury in steatotic rabbits. Twelve New Zealand White rabbits were fed a high-cholesterol (2%) diet. The control group (n=6) underwent lobar liver ischaemia for 1 h, followed by 6 h of reperfusion. In the treated group receiving NAC (n=6), an intravenous infusion of NAC was administered prior to and during the 6 h reperfusion period. Systemic and hepatic haemodynamics were monitored continuously. ALT (alanine aminotransferase) activity and bile production were measured. NMR spectroscopy was used to analyse bile composition. Oxidation of DHR (dihydrorhodamine) to RH (rhodamine) was used as a marker of production of reactive oxygen and nitrogen species. Moderate centrilobular hepatic steatosis was demonstrated by histology. The res...

British Journal of Surgery, 2004

Background N-acetylcysteine (NAC) may modulate the initial phase (less than 2 h) of liver warm is... more Background N-acetylcysteine (NAC) may modulate the initial phase (less than 2 h) of liver warm ischaemia–reperfusion (IR) injury but its effect on the late phase remains unclear. The present study investigated the role of NAC during the early and late phases in a rabbit lobar IR model. Methods Liver ischaemia was induced by inflow occlusion to the median and left liver lobes for 60 min, followed by 7 h of reperfusion. In the NAC group (n = 6), NAC was administered intravenously at 150 mg per kg over the 15 min before reperfusion and maintained at 10 mg per kg per h during reperfusion. In the IR group (n = 6), 20 ml 5 per cent dextrose was infused over the 15 min before reperfusion and continued at a rate of 10 ml/h. Animals in a sham operation group (n = 6) underwent laparotomy but no liver ischaemia. All animals were killed at the end of the experiment. Results Intracellular tissue oxygenation was improved after the second hour of reperfusion in animals treated with NAC compared wi...

Angiology, 2009

Femoral arterial lines are used for continuous monitoring of arterial blood pressure in experimen... more Femoral arterial lines are used for continuous monitoring of arterial blood pressure in experimental studies. However, placement of a catheter in the femoral artery could produce acute limb ischemia with associated systemic effects. The aim of this study was to investigate the effect of femoral arterial line insertion on liver function, in a rabbit liver lobar ischemia-reperfusion (I/R) model. Four groups of animals (n = 6 each) were studied: groups 1 and 2 (sham) underwent laparotomy but no liver ischemia. In groups 3 and 4 (I/R), liver lobar ischemia was induced for 60 minutes followed by 7 hours of reperfusion. In groups 1 and 3, the arterial line was placed in the femoral artery whereas in groups 2 and 4 in the ear artery. Liver function was assessed by serum alanine aminotransferase (ALT) activity, bile flow, plasma lactate levels, and histology. Results are expressed as mean ± SEM. Alanine aminotransferase activity and lactate levels were significantly higher in the I/R femora...