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J Kountouras

Publications and source records attributed to J Kountouras.

44 records · Page 3Linked to original sources

Metastatic liver disease of colorectal origin: the value of locoregional immunochemotherapy combined with systemic chemotherapy following liver resection. Results of a prospective randomized study.

BACKGROUND/AIMS: Liver resection for metastatic liver disease of colorectal origin, although considered as the 'gold standard' of treatment, is associated with limited long-term survival. The aim of this study was to compare overall survival, disease-free survival and the incidence of intra- or extrahepatic recurrence between patients who were randomly assigned to have locoregional chemoimmunotherapy with systemic chemotherapy group A (n = 62 patients) versus those who were treated with systemic immunochemotherapy group B (n = 60 patients). METHODOLOGY: Group A included patients who, after liver resection, received locoregional immunochemotherapy combined with systemic chemotherapy, while group B included patients who had undergone systemic immunotherapy combined with systemic chemotherapy following liver resection. The two groups were matched in terms of sex, age and stage of the disease. Prognostic factors and their impact on disease-free survival were studied in both groups. RESULTS: Two-year survival was 92% for group A versus 75% for group B, 5-year survival was 73% for group A versus 60% for group B. During the two-year period, 34% of the group A patients versus 52% of those of group B developed either intrahepatic or extrahepatic recurrence of the disease (P < 0.00212). CONCLUSIONS: From the analysis of the above results it becomes clear that regional immunochemotherapy combined with systemic chemotherapy leads to a decrease in the incidence of disease recurrence and thus to a significant prolongation of the overall survival and of disease-free survival.

Adult↗

Efficacy of trimebutine therapy in patients with gastroesophageal reflux disease and irritable bowel syndrome.

BACKGROUND/AIMS: GERD (gastroesophageal reflux disease) occurs in 25-51% of IBS (irritable bowel syndrome) patients. Trimebutine has been effective in some IBS patients by modulating colonic motility. Furthermore, it increases gastric emptying rates, and controls esophageal motility. The aim of this study was to investigate the efficacy of trimebutine therapy in GERD patients with IBS. METHODOLOGY: Sixty-nine patients with GERD and IBS underwent upper gastrointestinal endoscopic, histologic and clinical evaluation prior to and 3 months post-treatment. H. pylori presence was determined by histology and CLOtest. Forty patients (Group A) were treated with omeprazole plus trimebutine for 3 months: in 32 H. pylori-positive patients (subgroup A1), a standard triple eradication regimen was introduced. Twenty-nine patients (Group B) were treated with omeprazole for 3 months: in 24 H. pylori-positive patients (subgroup B1), the same eradication therapy was employed. RESULTS: Specialized intestinal metaplasia of the gastroesophageal junction was observed in 20% and in 17.2% of the patients in Groups A and B, respectively. Eradication rates were similar in subgroups A1 (84%) and B1 (83%). In Group A there was a significant improvement in GERD (P = 0.003) and IBS symptoms (P < 0.0001) as well as esophagitis (P = 0.029), when compared with Group B. CONCLUSIONS: Trimebutine appears to be effective in patients with GERD and IBS.

Adult↗

Locoregional immunochemotherapy in hepatocellular carcinoma.

Hepatocellular carcinoma remains a disease with a poor and dismal prognosis, and all forms of currently available conventional therapies are rarely beneficial. However, in recent years, combined targeting locoregional immunochemotherapy has been reported with very promising results. Adoptive immunotherapy with LAK cells (lymphokine-activated killer cells) and recombinant interleukin-2 is becoming one of the new modalities to reconstitute the depressed immune status of the tumor-bearing host. Interleukin-2, gamma-interferon, and interleukin-12 induce cytolytic activity of LAK and natural killer cells and are considered for cellular activation to locoregional immunotherapy before, after resection or even in unresectable hepatocellular carcinomas. Spleen is a suitable organ for LAK cell induction because it has densely packed lymphocytes. The strategy of administration of both interleukin-2 and gamma-interferon into the spleen for in vivo immunostimulation is based on the well-known synergism of the above cytokines. LAK cells have cytotoxic activity against a variety of tumor cells. In particular, LAK cells exhibit efficacy against lung and liver malignant lesions, as suggested by their trafficking pattern; activated killer cells injected i.v. into humans appeared in the lung early and were subsequently rapidly redistributed to the liver and spleen. Lipiodol-Urografin emulsion is probably an ideal cytokine/anti-cancer drug carrier suitable for the combined locoregional immunochemotherapy because during its preferential retention in the vascular network of the spleen and tumor, a gradual release of both immuno- and chemotherapeutical drugs bound to emulsion droplets is achieved ensuring a prolong half life for these drugs. Recent data point to the potential of considering intratumoral or intravascular use of adenovirus carrying interleukin-12 gene, and/or p53-based gene therapy as possible therapeutic strategies in patients with hepatocellular carcinoma.

Adjuvants, Immunologic↗

Effect of bacterial extracts on the immunologic profile in chronic relapsing brucellosis patients.

Brucellosis is an intracellular bacterial disease of common incidence in Greece. Existing therapy is inadequate and a considerable proportion of patients become chronically ill and are immunocompromised. Defects of the monocyte-macrophage system and T-lymphocytes have been described in chronic brucellosis and can be restored after immunopotentiation therapy. Bacterial (Klebsiella pneumoniae) extracts exert immunostimulating effects on the monocyte-macrophage system and have already been used successfully in the prevention of common infections of the respiratory track. So we decided to investigate: 1) Leukocyte Migration Index (LMI), 2) Monocyte-macrophage random and directed migration against both nonspecific leukoattractant (casein) and disease specific antigens (Brucella melitensis, Brucella abortus), 3) Monocyte-macrophage phagocytosis index, 4) Delayed-type hypersensitivity (skin tests) against seven antigens, before (TO), during (T2), and after (T3) oral administration of bacterial (Klebsiella pneumoniae) extracts at conventional doses plus antibiotics or not. Our results show that: 1) Concerning the LMI, 4 out of 19 remained anergic at time T3 of the study, 2) Random migration was not affected during treatment, 3) Directed migration increased significantly without reaching control group values, 4) Phagocytosis index increased significantly and reached normal values at T3, 5) Delayed type hypersensitivity reactions (skin tests) increased significantly at the end of the study period. Reaction against Tuberculin and Candida antigens showed the most pronounced increase in skin reactivity. In conclusion, bacterial (Klebsiella pneumoniae) extracts improve peripheral monocyte locomotion and restore phagocytosis index, thus enhancing cellular immunity parameters in immunocompromised chronic brucellosis patients.

Journal Article↗

Value of serum protective activity against acid precipitation of poly (U) in the differentiation between cirrhotic patients with and without hepatocellular carcinoma.

The serum protective activity against acid precipitation of poly (U) and a-fetoprotein levels were compared in 39 cirrhotic patients with hepatocellular carcinoma (HCC) and in 33 patients with chronic liver disease (CLD) alone, in order to differentiate malignant and nonmalignant chronic liver disease. All but one (97.4%) patients with HCC were found to have serum protective activity levels of greater than or equal to 21 micrograms/ml, whereas all but one (97%) patients with CLD had serum protective activity levels of less than or equal to 20 micrograms/ml. Mean serum protective activity levels were significantly higher in the HCC group than in those with CLD (p less than 0.0001). Serum a-fetoprotein concentrations of over 500 ng/ml, suggesting malignancy, were observed in 54% of patients with HCC and in 15% of patients with CLD. Application of the best discriminating values for protective activity (greater than 21 micrograms/ml) and for a-fetoprotein (greater than 500 ng/ml) to 72 patients with or without HCC revealed an efficiency of 97.2% for protective activity and only 68.1% for a-fetoprotein.

Adult↗

Value of ascitic fluid ferritin in the differential diagnosis of malignant ascites.

The ascitic fluid ferritin concentrations were compared with serum-ascites albumin gradient (SAAG), in their diagnostic ability for detection of malignancy in 60 patients with ascites: 29 with chronic liver disease alone (CLD) and 31 patients with various neoplasms. Of the patients with malignancy, 12 had liver metastases, 9 had no evidence of liver involvement, and 10 had hepatocellular carcinoma (HCC) with or without coexisting liver cirrhosis. Analysis of our data confirms that the ascitic ferritin is a more accurate indicator of malignant ascites (MA) than the SAAG. This new parameter is particularly helpful in distinguishing MA associated with HCC and/or metastatic liver disease from nonmalignant ascites due to CLD alone.

Ascites↗

Interferon-A 2a administration in chronic anergic brucellosis.

Two cases with chronic anergic brucellosis are described. Both patients suffered repeated disease relapses and responded poorly to conventional treatment. The immunologic research revealed that both patients were anergic to brucella antigens and immunocompromised. In an effort to restore patients' defective immune responses, we administered Interferon-A 2a during a six month treatment period as follows: a) loading dose- 3MU SC 3 days/week for an 8 week trial, followed by, b) maintenance period- 3MU SC three times/week. Our results showed that IFN administration induced clinical remission in both patients by the end of the 4th month of treatment. Additionally, Coombs' agglutination titers decreased gradually, the leucocyte migration index and the skin tests developed "energy" to antigens and the monocyte macrophage function tests were restored to normal. We concluded that IFN treatment can be beneficial in chronic anergic brucellosis by restoring defective immune responses, promoting therefore a sufficient inflammatory response against brucella infection.

Adult↗

In vivo effect of granulocyte-macrophage colony-stimulating factor and interferon combination on monocyte-macrophage and T-lymphocyte functions in chronic hepatitis B leukocytopenic patients.

BACKGROUND/AIMS: Both rhGM-CSF and IFN-gamma have antiviral and immunoregulatory effects. Furthermore, GM-CSF has the advantage of increasing WBC in leukocytopenic patients. METHODOLOGY: We investigated a) the antiviral effects of rhGM-CSF and INF-alpha combination treatment in 12 chronic hepatitis B patients with leukocytopenia as a result or not of previous interferon therapy, b) the in vivo effects of these agents on monocyte-macrophage and T-lymphocyte functions and, c) their correlation to HBV infection outcome. RESULTS: Combination therapy caused a significant fall in HBV-DNA levels (p<0.0002), accompanied by significant reductions in transaminase levels and in histological activity index (p<0.0001, in each case). In parallel, rhGM-CSF induced a 2.7- to 5-fold weekly increment in WBC. Moreover, treatment caused a significant increase in all monocyte-macrophage parameters (p<0.0001 for random, directed migration and phagocytosis index) and in peripheral blood lymphocyte parameters (p<0.0001 for IL-2r and HLA-DR expression) studied. A similar picture was also obtained from cytokine levels (IL-2 and GM-CSF) in the supernatants from PHA-cultured T-lymphocytes (p<0.0003, <0.001, respectively). CONCLUSIONS: The combined therapy achieves the initial treatment aim of increasing WBC and exerting an antiviral effect. In addition, the observed changes in immunological parameters probably reflect a Th1 pattern of immune response that could be responsible for the fate of HBV infection. Finally, cytokine levels (IL-2 and GM-CSF) in the supernatants might serve to monitor viral activity and outcome of the HBV infection.

Adult↗