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Christos Zavos

Publications and source records attributed to Christos Zavos.

At least 37 records · Page 2Linked to original sources
PubMed2005

Apoptotic and anti-angiogenic strategies in liver and gastrointestinal malignancies.

Inappropriate suppression of apoptosis is strongly implicated in tumorigenesis. Tumor development is heralded by the mutation of tumor suppressor genes and overexpression of anti-apoptotic genes permitting cell survival. Thus, inducing the apoptotic process in various ways can be applied to cancer management. Besides, angiogenesis is a crucial process for tumor growth and metastasis. New strategies targeting fundamental play-markers of the angiogenic process are currently under investigation.

Angiogenesis Inhibitors↗
PubMed2005

New molecular concepts of Barrett's esophagus: clinical implications and biomarkers.

Barrett's esophagus (BE) represents the most serious histological consequence of gastroesophageal reflux disease (GERD) that develops in 5-10% of patients with GERD. Given that BE is the only known precursor to esophageal adenocarcinoma (EA), a systematic endoscopic biopsy protocol can detect EAs at an early stage. However, endoscopic and histopathological evaluation of BE are not adequate for effective screening of high risk patients. Therefore, molecular abnormalities associated with BE have been considered as surrogate markers and their use as such is proposed. Flow cytometry is the most useful adjunct to histology, and ploidy status of BE is an independent risk factor. Cyclin D1 overexpression is inversely correlated with survival in EA. C-erbB2 (+) patients have poorer prognosis. High plasma adenomatous polyposis coli levels correlate with reduced patient survival. p53 expression allows patient risk for EA stratification. Nuclear factor-kappaB overexpression inversely correlates with good response to adjuvant chemotherapy and radiotherapy in EA. Patients with cyclooxygenase-2 overexpression have reduced survival rates. Increased E-cadherin staining is associated with shorter survival in EA patients who received chemoradiotherapy. Finally, existing data cannot rule out a correlation between EA and colorectal tumors. Seventeen BE molecular alterations yielded noteworthy clinical implications. Apart from endoscopy and histology, these data allow for better risk stratification for patients with BE and for more efficient and timely therapeutic approaches.

Adenocarcinoma↗
PubMed2005

High-dose allopurinol for prevention of post-ERCP pancreatitis: a prospective randomized double-blind controlled trial.

BACKGROUND: Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP. Allopurinol, a xanthine oxidase inhibitor that blocks generation of oxygen-derived free radicals, potentially may prevent post-ERCP pancreatitis. This study assessed the efficacy of high-dose oral allopurinol for prevention of post-ERCP pancreatitis. METHODS: A prospective, double-blind, placebo-controlled trial was conducted in 250 patients undergoing ERCP. Patients were randomized to receive allopurinol (600 mg) or placebo orally at 15 and 3 hours before the procedure. Patients were clinically evaluated, and serum amylase levels were determined before ERCP and at 6 and 24 hours thereafter. Standardized criteria were used to diagnose and to grade the severity of post-ERCP pancreatitis. RESULTS: A total of 243 patients were included in the analysis. The two groups were similar with regard to age; gender; underlying disease; indication for treatment; ERCP findings; and type of treatment, except for biliary sphincterotomy. Only 43 patients in the allopurinol group underwent biliary sphincterotomy vs. 87 in the placebo group ( p < 0.001). The frequency of acute pancreatitis was significantly lower in the allopurinol vs. the placebo group in the final multinomial regression analysis: allopurinol group, 4/125 (3.2%), with all 4 cases graded as mild, vs. placebo group, 21/118 (17.8%), of which 8/118 (6.8%) were graded as mild, 11/118 (9.3%) as moderate, and 2/118 (1.6%) as severe with fatal outcome ( p < 0.001). The protective effect of allopurinol was also apparent in the diagnostic ERCP and the biliary sphincterotomy subgroups when the frequency of post-ERCP pancreatitis was analyzed after stratification by procedure. The mean duration of hospitalization for pancreatitis was significantly shorter in the allopurinol compared with the placebo group (2.5 vs. 5.67 days; p < 0.001). CONCLUSIONS: Pretreatment with high-dose, orally administered allopurinol decreases the frequency of post-ERCP pancreatitis. Despite the promising results of this prospective, randomized trial, further studies are needed to verify these observations before allopurinol can be recommended for routine clinical use.

Adult↗
PubMed2005

Intravenous N-acetylcysteine does not prevent post-ERCP pancreatitis.

BACKGROUND: Acute pancreatitis remains the most common complication of ERCP. Prophylactic administration of N-acetylcysteine (NAC) probably decreases the incidence and the severity of experimental pancreatitis. The aim of the present study was to assess the efficacy of intravenous NAC for prevention of post-ERCP pancreatitis in humans, who represent an appropriate model to study the potential role of NAC in this setting. METHODS: A prospective, double-blind, placebo-controlled trial was conducted in 256 patients who underwent ERCP. Patients were randomized to receive intravenous NAC at a loading dose of 70 mg/kg 2 hours before and 35 mg/kg at 4-hour intervals for a total of 24 hours after the procedure, or to receive normal saline solution as placebo. Patients were clinically evaluated, and serum amylase levels were measured before and 6 hours and 24 hours after the procedure. Standardized criteria were used to diagnose and to grade the severity of post-ERCP pancreatitis. RESULTS: A total of 249 patients were included in the analysis. The two groups were matched for age, gender, underlying disease and indication for treatment, ERCP findings, and type of treatment. The overall incidence of post-ERCP acute pancreatitis was 10.8%, with 12.1% in the NAC group and 9.6% in the placebo group. There were no statistical differences in the incidence or severity grades between the groups. The mean duration of hospitalization for pancreatitis also was similar in the NAC group and the placebo group (3.6 +/- 0.9 and 3 +/- 1.5 days, respectively). CONCLUSIONS: The results of this trial show the absence of any beneficial effect of NAC on the incidence and the severity of ERCP-induced pancreatitis.

Adult↗
PubMed2005

Non-invasive cardiologic findings in patients with malignant melanoma*.

Although malignant melanoma has a great propensity (38-50%) for cardiac involvement, as indicated by autopsy findings, cardiac metastases are rarely identified ante-mortem. The aim of this study was to record abnormal electrocardiographic and echocardiographic findings in patients with malignant melanoma. One hundred and eighty-five consecutive patients (male/female, 99/86; mean age, 59.6 years) with histologically proven malignant melanoma (American Joint Committee on Cancer stages II-IV), and with no known history of heart disease, were evaluated prospectively over a period of 11 years. The cardiologic findings considered were an unexpected delayed conduction of an electrical stimulus, recorded by high-resolution signal-averaged electrocardiogram (presence of ventricular late potentials), prolongation of the PR, QRS and QTc segments in a surface electrocardiogram, and abnormal Q waves. Echocardiographic findings comprised pericardial implantation/effusion or presence of intracavitary/intramyocardial metastases. Forty-one abnormal findings were recorded, pertaining to 38 of the 185 patients (19.5%). In particular, PR interval prolongation was found in eight patients (4.3%) and QTc interval prolongation in 11 (6%). Abnormal Q waves were recorded in five patients (2.7%). The filtered QRS interval was prolonged in seven patients (3.8%). Finally, echocardiographic examination showed discrete pericardial implantations and small to moderate pericardial effusion in six patients (3.2%) and intracavitary/intramyocardial metastases in four (2.1%). The median survival of these patients was 33 months (95% confidence interval, 19.9-46.1 months). It can be concluded that abnormal electrocardiographic and echocardiographic findings are recorded at the time of diagnosis of the disease in a significant percentage of patients with malignant melanoma.

Echocardiography↗
PubMed2004

Induction of apoptosis as a proposed pathophysiological link between glaucoma and Helicobacter pylori infection.

Although apoptosis is equally important both for the development and for the maintenance of homeostasis in some adult tissues, it can also be associated with disease processes. Current studies indicate that apoptosis is a mechanism of cell death in several important ocular and gastrointestinal diseases including glaucoma, and Helicobacter pylori (H. pylori)-induced upper gastrointestinal disorders and/or extraintestinal diseases, including autoimmune and neurodegenerative ones (Sjögren's syndrome, Guillain-Barre syndrome or Parkinson's disease). Glaucoma is also associated with similar autoimmune and neurodegenerative disorders, characterized by apoptotic loss of specific populations of neurons. Recently, a high prevalence of H. pylori infection has been recognized in patients with chronic open-angle glaucoma. In addition, H. pylori eradication may positively influence glaucoma parameters, thereby suggesting a possible causal link between H. pylori and glaucoma. H. pylori infection may influence the pathophysiology of glaucoma by releasing various proinflammatory and vasoactive substances, as well as by influencing apoptotic process; parameters that may also exert their own effects in the induction and/or progression of glaucomatous neuropathy. Importantly, H. pylori infection and glaucoma share the Fas/FasL and the mitochondria-mediated apoptotic pathways, thereby proposing an apoptotic link in the pathophysiology of both diseases.

Apoptosis↗
PubMed2004

A hypothesis on the role of insulin-like growth factor I in testicular germ cell tumours.

It has already been established that the growth effects of growth hormone (GH) are mediated through insulin-like growth factor I (IGF-I). Recent studies demonstrated a relationship between IGF-I levels and various types of cancer, namely colon, prostate, breast, brain and lung cancer. In addition, many experimental observations documented a participation of the IGF-I system in tumourigenesis through enhanced cell proliferation rate, anti-apoptotic functions and stimulation of neovascularization. With the present known biological mechanisms, implicated in the pathogenesis of testicular germ cell tumours (GCT), it is difficult to interpret the consistently increasing incidence of this tumour over the last decades. On the other hand, unpublished data of our department are in accordance with previous published studies, suggesting that GCT may be positively associated with body height. Scattered publications report development of GCT secondary to acromegaly or long-term GH replacement therapy. Thus, it is possible that the IGF-I system may be implicated in this pathogenesis, thereby predisposing to an increased risk of testicular GCTs. If IGF-I and IGFBP-3 are found to correlate with a high incidence of testicular GCT, they might be useful surrogate markers for diagnosis and surveillance of tumour growth, and an early screening method to identify an increased risk of this type of cancer in the first degree young male relatives of these patients.

Animals↗
PubMed2004

Apoptosis and autoimmunity as proposed pathogenetic links between Helicobacter pylori infection and idiopathic achalasia.

Achalasia is a disorder of the oesophagus characterised by increased lower oesophageal sphincter (LOS) tone, lack of LOS relaxation with swallowing and aperistalsis of the body of the oesophagus. The aetiology and pathogenesis of idiopathic achalasia are still unclear, although a viral cause, genetic influences (associations with HLA loci) and autoimmune processes have been postulated. Degeneration and significant loss of nerve fibres, associated with an inflammatory infiltrate of the myenteric plexus in idiopathic achalasia, provide evidence of an immune mediated destruction of the myenteric plexus, possibly through apoptotic process. This concept is reinforced by the concomitant appearance of achalasia and Guillain-Barré syndrome (GBS) and/or Parkinson's disease, where inappropriate initiation of apoptosis has been proposed to underlie the neuronal attrition. In the same respect, Helicobacter pylori (H. pylori) infection has been associated with gastric autoimmunity, and patients infected with H. pylori have been shown to possess autoantibodies that cross-react with antigens expressed on the gastric mucosa. Furthermore, H. pylori is thought to be associated with the development of autoimmune sequelae observed in peripheral neuropathies and GBS, where autoantibodies to specific neural targets have been found to impair native neural function by inducing nerve tissue damage, possibly by apoptosis. Taken together, we assume that H. pylori infection might be a pathogenetic factor of achalasia through induction of autoimmunity and apoptosis. Whether eradication of H. pylori infection may indirectly offer benefit to the pathophysiology of idiopathic achalasia by ameliorating the apoptotic loss of ganglion cells and their axons in the oesophageal wall remains to be elucidated.

Animals↗
PubMed2003

Increased levels of Helicobacter pylori IgG antibodies in aqueous humor of patients with primary open-angle and exfoliation glaucoma.

PURPOSE: A prospective, nonrandomized, comparative study was carried out to investigate the levels of anti- H. pylori-specific IgG antibodies in the aqueous humor and serum of patients with primary open-angle glaucoma (POAG) and patients with exfoliation glaucoma (XFG), and to compare them with those in age-matched cataract patients. METHODS: Aqueous humor was aspirated at the beginning of glaucoma surgery from 26 eyes of 26 patients with POAG, 27 eyes of 27 patients with XFG, and at the beginning of phakoemulsification cataract surgery from 31 eyes of 31 age-matched normotensive cataract patients. Serum samples were obtained the day before surgery from all patients. Anti- H. pylori IgG concentration in the aqueous humor and serum was measured by means of an enzyme-linked immunosorbent assay. RESULTS: The mean concentration (+/- SE) of anti- H. pylori-specific IgG was significantly greater in the aqueous humor samples from patients with POAG (14.27+/-3.86 U/ml) and XFG (14.25+/-3.39 U/ml) than in those from age-matched control cataract patients (4.67+/-1.07 U/ml); ( P=0.006 and P=0.003, respectively). No difference was observed in the levels of H. pylori-specific IgG antibodies between POAG and XFG aqueous humor samples ( P=0.5). Similarly, the serum concentration of anti- H. pylori antibodies was significantly greater in patients with POAG (69.96+/-9.69 U/ml; P=0.013) and XFG (81.37+/-10.62 U/ml; P=0.002) than in the cataract controls (44.16+/-6.48 U/ml). The mean vertical cupping correlated significantly with the titer of anti- H. pylori-specific IgG in the aqueous humor in the POAG patients. CONCLUSION: H. pylori-specific IgG antibody levels are significantly increased in the aqueous humor and serum of patients with POAG and XFG. Moreover, the titer of anti- H. pylori antibody in the aqueous humor might reflect the severity of glaucomatous damage in POAG patients. These findings support a role for H. pylori infection in the pathobiology of these two common glaucomas.

Adult↗