Ozlem Erdem

Effects of vitamin E treatment on peroxisome proliferator-activated receptor-α expression and insulin resistance in patients with non-alcoholic steatohepatitis: results of a pilot study

Background: Insulin resistance (IR) is commonly associated with non‐alcoholic steatohepatitis (NASH). Peroxisome proliferator‐activated receptor‐α (PPAR‐α) may also play a role in the pathogenesis of NASH. A pivotal role in NASH pathogenesis depends on the hypothesis of increased oxidative stress. The aim of our study was to evaluate the effects of supplemental oral vitamin E, a potent antioxidant, on liver functions, PPAR‐α expression and IR in patients with NASH.

Angiogenesis, p53, and bcl-2 expression as prognostic indicators in endometrial cancer: Comparison with traditional clinicopathologic variables

&NA; We investigated the relation of expression of tumor‐suppressor gene product p53, apoptosis‐regulator gene product bcl‐2, and CD34 (as a measure of microvessel density [MVD]) with traditional clinicopathologic prognostic variables in endometrial carcinoma (histologic type, grade, depth of myometrial invasion, angiolymphatic invasion, lymph node involvement). In specimens from 63 patients with endometrial carcinoma, the mean MVD (64.38±28.71 microvessels per 200× field) was not related to any clinicopathologic variables. Nuclear p53 expression was detected in 15 (23.8%) patients and was higher in nonendometrioid carcinomas (p<0.05) and in tumors with increasing histologic grade (p<0.001). Cytoplasmic bcl‐2 staining was seen in 79.3% of the tumors. There was a negative correlation between bcl‐2 expression and histologic type and tumor grade (p<0.05). In survival analysis, patient age, FIGO stage, high expression of p53, low expression of bcl‐2, and high and intermediate MVD values were found to be the most significant prognostic indicators of survival (p<0.05). In multivariate regression analysis, FIGO stage and low bcl‐2 expression were found to be the only independent indicators of prognosis (p<0.05).

Urgent Laparoscopic Cholecystectomy Is the Best Management for Biliary Colic

Background/Aim: Delay of laparoscopic cholecystectomy after the diagnosis of biliary colic may increase the probability of recurrent emergency admission while awaiting elective cholecystectomy. The aim of this study was to compare the possible advantages and safety of urgent laparoscopic cholecystectomy (ULC) with elective laparoscopic cholecystectomy (ELC) in patients with biliary colic. Patients and Methods: Between 2001 and 2003, 75 patients with biliary colic were included in this study. The patients were classified into following two groups: patients who had ULC in 24 h were in group I (n = 28) and patients who had ELC (mean interval 4.22 ± 1.42 months) were in group II (n = 35). Conversion to open cholecystectomy, operative time, postoperative hospital stay, costs, and complications were evaluated. Results: In group II, 9 patients made a total of 13 return visits to the emergency department with recurrent attacks of biliary colic or complications of gallstone disease. Mean operative time increased from 35.1 ± 6.74 min for urgent laparascopic cholecystectomy to 49.9 ± 6.12 min for ELC (p > 0.05) and hospital stay time increased from 1.06 ± 0.4 to 2.31 ± 2.36 days (p < 0.05). Conversion to open cholecystectomy increased from 0% in group I to 17.2% in group II (p < 0.05). Discussion: ULC for biliary colic may be the most medically efficacious and cost-effective treatment.

Dermatofibrosarcoma protuberans treated with wide local excision and followed at a cancer hospital: prognostic significance of clinicopathologic variables.

Dermatofibrosarcoma protuberans (DFSP) is a relatively rare low-grade sarcoma. Local control can usually be achieved by wide local excision, but some patients still develop recurrences. The aim of this study was to investigate the correlation between clinicopathologic factors and recurrence-free survival (RFS)/overall survival (OS) in a large series of DFSP patients from a single institution. The study group included sections and medical records of 122 patients (63 women and 59 men, median age of 43) with primary DFSP from UT-MD Anderson Cancer Center between 1976 and 2005. Fibrosarcomatous change was detected in 24 (20.9%) patients. Thirty-eight of 120 patients (31.7%) recurred with a median RFS of 10.2 years. The 5-year RFS rate was 64.2%. Based on univariate analyses, fibrosarcomatous change, mitotic count, metastasis at time of diagnosis, and acral location were significantly associated with shorter RFS. On multivariate analysis, acral location and fibrosarcomatous change remained significant for shorter RFS. Five-year OS was 95.5% (95% confidence interval: 75.42%–99.3%). On univariate analysis, mitotic count per square millimeter, presence of necrosis, and metastasis at time of diagnosis were significantly associated with lower OS. On multivariate analysis, only presence of metastasis remained significantly associated with shorter OS. DFSP-FS variant and acral site are associated with shorter recurrence-free interval after wide local excision. Therefore, patients with tumors on acral sites or those with a fibrosarcomatous component may benefit from aggressive therapies other than wide local excision. The only factor that remains significantly associated with decreased OS is detection of metastasis.

Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study

BackgroundPeroxisome proliferators-activated receptor alpha (PPARα) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPARα agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis.MethodsForty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation (BDL), III = BDL + vehicle (gum Arabic), IV = BDL + fenofibrate (100 mg/kg/day). All rats were sacrificed on 7th day after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), gamma-glutamyl transferase, (GGT), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1 β), and total bile acid (TBA) in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining.ResultsFenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-α, IL-1 β levels, and TBA (P < 0.01). Hepatic portal inflammation, hepatic necrosis, number of the bile ducts and apoptosis in rats with BDL were more prominent than the sham-operated animals (P < 0.01). PPARα induction improved all histopathologic parameters (P < 0.01), except for the number of the bile duct, which was markedly increased by fenofibrate therapy (P < 0.01).ConclusionShort-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.

A comparison of the local effectiveness of mitomycin C, aprotinin, and Adcon-L in experimental peridural fibrosis

BACKGROUND Peridural fibrosis and leptomeningeal adhesion formation are among the common causes of FBSS. Various materials have been used to prevent the compressive effect of postoperative PF on neural structures. We investigated and compared the effects of 3 agents--aprotinin, mitomycin C, and Adcon-L--to PF after lumbar laminectomy in rabbits. METHODS Four groups each including 8 rabbits were formed: Adcon-L, aprotinin, mitomycin C, and control groups. L3 laminectomy was performed on each animal. One of the 3 agents was administered locally to laminectomy areas in each group. All the animals were killed 4 weeks after the surgery. Peridural fibrosis, arachnoidal fibrosis, and dural adhesions were evaluated histologically and graded. The results were compared statistically by using a standard chi2 test. RESULTS There were significant differences in the PF grades among the experimental groups and the control group (P < .05). When the fibroblast density and the inflammatory cell density were evaluated, the grades of the experimental groups were better compared with the grades of the control group, but the difference was not statistically significant (P > .05). CONCLUSION Various materials have been used to prevent the compressive effect of postoperative PF on the neural structures. Aprotinin, mitomycin C, and Adcon-L are effective in preventing PF and dural adhesions in postlaminectomy areas. However, mitomycin C and Adcon-L were more effective than aprotinin in preventing peridural scarring.

The role of frozen section evaluation in the diagnosis of adnexal mass

The purpose of this study was to evaluate the accuracy of frozen section diagnosis in patients who were subjected to the exploratory laparotomy for pelvic mass. Overall, 207 patients were included in this study and the mean age of the patients was 50.9 ± 14.9 years (range, 18–84 years). Of these patients, 98 (47%) had benign, 16 (8%) had borderline, and 93 (45%) had malignant histologies at permanent section. The diagnosis at frozen section was deferred for three patients (1.4%) and these patients were excluded from the further analyses. The overall discordance rate was 5.3%. To calculate the sensitivity and specificity values, 2 × 2 contingency tables were constructed in two ways. In the first calculation, borderline histology was considered malignant, and the sensitivity and specificity rates were 97% and 92%, respectively. In the second analysis, it was accepted as benign, and these values were 100% and 98%, respectively. To determine the possible factors related with discordant diagnoses, age, menopausal status, tumoral size, laterality of tumors, and histologic diagnoses were analyzed. Significant association was noted for size and borderline and mucinous histologies. In patients with borderline histology, the discordance rate was 40%. This value for the remaining patients was 3.2% (P< 0.001). The rate of misdiagnosis was 17.4% for mucinous tumors, whereas it was 4.8% for the remaining epithelial tumors (P= 0.03). Frozen section evaluation revealed high sensitivity and specificity values in this study. To increase the accuracy of diagnosis, further diagnostic markers are needed especially for patients with large lesions, borderline tumors, and mucinous histologies.

Expression of vascular endothelial growth factor and assessment of microvascular density with CD 34 and endoglin in proliferative endometrium, endometrial hyperplasia, and endometrial carcinoma

The aim of this study was to compare vascular endothelial growth factor (VEGF), CD 34, and endoglin expressions as markers of angiogenesis in proliferative endometrium (PE), endometrial hyperplasia (EH), and endometrial carcinoma (EC) and to find the possible impact of angiogenesis on malign transformation. Formalin-fixed, paraffin-embedded tissues from 12 patients with PE, 23 patients with simple EH and complex EH with atypia, and 31 patients with EC were included. A semiquantitative scoring system was used to assess the intensity and degree of staining of VEGF. Microvessel density (MVD) was assessed with endoglin and anti-CD 34 in most vascular areas. VEGF expression was significantly higher in EC and EH than PE, but there was no difference between EC and EH. According to CD 34 staining, there were no differences in MVD between groups. However, mean MVD counts assessed by endoglin were significantly higher in EC than PE and EH. Although VEGF expression in EC was significantly higher, it did not correlate with other measures of angiogenesis. MVD using endoglin seemed to reflect neoplastic angiogenesis better than CD 34

Comparison of the clinical value of CA 19-9 versus CA 125 for the diagnosis of endometriosis

Preoperative blood samples and intraoperative tissue specimens were obtained from 101 patients with endometriosis and 78 patients without endometriosis referred for benign gynecologic operations to investigate the clinical value of serum and tissue CA 19-9 levels in the diagnostic evaluation of endometriosis as compared to CA 125. Our prospective cohort study showed that serum CA 19-9 is a valuable marker in the diagnosis of endometriosis, and it may be used to predict the patients with severe endometriosis when used with CA 125.

Importance of cytokines, oxidative stress and expression of BCL-2 in the pathogenesis of non-alcoholic steatohepatitis

Objective. Non-alcoholic steatohepatitis (NASH) is a form of chronic hepatitis. The pathogenesis of NASH has been dealt with in only a few studies and so it has not been clearly identified yet. The purpose of this study was to investigate the roles of TNF-α, TGF-β, IL-6, IL-8, malondialdehyde (MDA), nitric oxide (NO) and the expression of Bcl-2 and Bax in the pathogenesis of NASH. Material and methods. The study included 92 patients, 57 of whom were diagnosed with biopsy-proven NASH, 13 with biopsy-proven hepatosteatosis and 22 with ultrasonography-diagnosed hepatosteatosis. Serum levels of TNF-α, TGF-β, IL-6 and IL-8 were measured using the ELISA method. The plasma levels of NO were studied using the Griess method. Expressions of Bcl-2 and Bax were examined in paraffin blocks of liver biopsy materials by means of immunohistochemical-staining. MDA levels were measured using the thiobarbituric acid method. Results. No significant difference was found in the levels of TNF-α, TGF-β, IL-6 or NO between the three groups (p>0.05). No difference was found in expression of Bcl-2 and expression of Bax between the biopsy-proven NASH and biopsy-proven hepatosteatosis groups (p>0.05). In the NASH group, the levels of IL-8 and MDA were found to be higher than those in the hepatosteatosis groups (p<0.05). Conclusions. The elevated levels of MDA may indicate the relationship between oxidative stress and NASH. Furthermore, IL-8 was found to be higher in the NASH group than in the hepatosteatosis group, demonstrating the importance of inflammation in the pathogenesis of NASH.