ABSTRACT
Approximately 30% of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs) genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS). Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations. We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4) genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR) and A-Bw4 (ligand for inhibitory KIR3DL1) were observed more frequently (p=0.017 and p=0.024); and KIR2DS2 and KIR2DS3 (both activating KIRs) were observed less frequently (p=0.005 and p=0.043). Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS) (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07). The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023). KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI = 0.080-0.863, p=0.028). The number of activating KIRs are correlated strongly with DFS, none/ one/ two KIR : 54/77/98 months (p=0.004). In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs, independent of tumor localization or stage, is associated with long-term DFS.
Subject(s)
Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Genotype , Neoplasm Recurrence, Local/genetics , Aged , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Disease-Free Survival , Female , Follow-Up Studies , HLA-B Antigens/genetics , HLA-B Antigens/metabolism , HLA-C Antigens/genetics , HLA-C Antigens/metabolism , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Prognosis , Receptors, KIR/genetics , Receptors, KIR/metabolism , Receptors, KIR2DL1/genetics , Receptors, KIR2DL1/metabolism , Receptors, KIR3DL1/genetics , Receptors, KIR3DL1/metabolism , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND/AIMS: Hepatic ischemia reperfusion injury induced by Pringle maneuver leads to bacterial translocation, endotoxemia and apoptosis. Our aim was to compare the effects of low and high dose dexamethasone pretreatment on antioxidant enzyme activities, bacterial translocation, endotoxemia and apoptosis, following Pringle maneuver. METHODOLOGY: Thirty-two rats were randomized into four groups; sham, control and two treatment groups; low dose dexamethasone (0.1 mg/kg) and high dose dexamethasone (1 mg/kg). In the treatment groups dexamethasone was administered intraperitoneally one hour before Pringle maneuver. Twenty-four hours after closing rats' abdomen, re-laparotomy was performed and tissue samples were taken from the mesenteric lymph nodes, liver, ileum and spleen and 1 mL of blood was drawn from the aorta. Bacterial translocation, endotoxemia, apoptosis and enzyme activities of G6PD, 6-PGD, GR, GST, GPx and CAT were evaluated. RESULTS: Low dose dexamethasone significantly decreased bacterial translocation to mesenteric lymph nodes, and reduced liver and enterocyte apoptosis, whereas high dose dexamethasone caused only a significant reduction in enterocyte apoptosis (p<0.05). Dexamethasone both in low and high doses significantly reduced the decrease in antioxidant enzyme levels (p<0.05). CONCLUSIONS: Low dose dexamethasone pretreatment caused constructive therapeutic effects after Pringle maneuver, whereas these effects were seen partially with a high dose.
Subject(s)
Dexamethasone/therapeutic use , Hepatectomy/methods , Liver/blood supply , Reperfusion Injury/prevention & control , Animals , Apoptosis/drug effects , Bacterial Translocation/drug effects , Catalase/metabolism , Hemostasis, Surgical/methods , Male , Pentose Phosphate Pathway , Rats , Rats, Sprague-DawleyABSTRACT
Cystic echinococcosis is endemic in certain parts of the world. The growth of the cyst is often slow, and the liver and lungs are the most frequently involved organs. Diagnosis is based on clinical signs and symptoms and epidemiological data, while ultrasonography is important for the classification of hydatid cysts. Although certain types of hydatid cysts are successfully treated by percutaneous aspiration, injection, and reaspiration, surgery remains the treatment of choice. We reviewed the current trends in the diagnosis and management of cystic echinococcosis, with special emphasis on hepatic and pulmonary involvement.
