Mutlu Hayran

Cystic and adenofibromatous clear cell carcinomas of the ovary: distinctive tumors that differ in their pathogenesis and behavior: a clinicopathologic analysis of 122 cases.

Ovarian clear cell carcinomas (CCC) typically present as large adnexal, stage I tumors and are generally considered highly malignant. They are frequently associated with endometriosis and, less often with clear cell adenofibromas. We hypothesized that CCCs are a heterogeneous group of tumors, some arising from a cyst and others from an adenofibroma. To test this hypothesis, 122 cases of CCC were retrieved from the surgical pathology files of National Taiwan University Hospital (74), The Johns Hopkins Hospital (23), and Serei Mikatahara General Hospital (23) (1985 to 2006). Cases were divided into 3 subgroups: (1) cystic, (2) adenofibromatous, and (3) indeterminate. Various features were analyzed including: age, race, laterality, tumor size, architectural pattern (papillary, tubulo-cystic, solid, mixed patterns), grade, mitotic index, association with endometriosis including atypical endometriosis/intraepithelial carcinoma, stage and survival. Nearly 70% of all the patients were diagnosed as stage I. The 2-year and 5-year survival (all stages) was 78% and 68%, respectively. Striking clinicopathologic differences were observed between cystic and adenofibromatous CCCs. Cystic CCC was more frequently diagnosed as stage I compared with adenofibromatous CCC (75% vs. 44%). Conversely, adenofibromatous CCCs were diagnosed more often in advanced stages (stages II-IV) compared with cystic CCCs (56% vs. 18%). Both the cystic and adenofibromatous CCC forms were associated with endometriosis and atypical endometriosis/intraepithelial carcinoma, but the frequency was much higher in the cystic group. Specifically, endometriosis was found in 91% of cystic CCCs and atypical endometriosis/intraepithelial carcinoma in 62% of these cases, whereas endometriosis was found in 44% of adenofibromatous CCCs and atypical endometriosis/intraepithelial carcinoma in 11% of cases. A predominantly papillary pattern was seen in 47% of cystic CCCs, whereas none of the adenofibromatous carcinomas displayed a predominantly papillary pattern. A more favorable outcome was observed for cystic CCCs compared with adenofibromatous CCCs (all stages) which was accounted for by the high proportion of stage I tumors. The 2-year and 5-year survival for the cystic CCCs was 82% and 77% and for the adenofibromatous CCCs (all stages), 62% and 37%, respectively. In summary, subdividing ovarian CCCs into cystic and adenofibromatous CCC reveals differences in a number of clinicopathologic features including their association with endometriosis, histologic patterns, stage distribution, and clinical behavior. Because there were a relatively small number of adenofibromatous CCCs in this series, additional cases must be studied to confirm these findings.

Relation between epicardial fat thickness and coronary flow reserve in women with chest pain and angiographically normal coronary arteries

OBJECTIVE A significant proportion of women with angina-like chest pain and angiographically normal coronary arteries have microvascular dysfunction as detected by reduced coronary blood flow reserve (CFR). Classical clinical risk factors of atherosclerosis poorly predict this scenario. We sought to assess whether increased epicardial fat tissue, which is a metabolically active organ, could be associated with impaired CFR in these patients. METHODS We enrolled 68 women who underwent coronary angiography and had no obstructive coronary artery disease. Data about classical risk factors, insulin resistance and serum levels of C-reactive protein (CRP) and adiponectin were obtained. Stress tests were evaluated. Coronary flow velocities at baseline and under-induced hyperemia and epicardial fat thickness (EFT) were measured by transthoracic echocardiography within 48 h of angiography. CFR >or=2.0 was considered normal. RESULTS Forty percent of women had reduced CFR suggestive of microvascular dysfunction and 60% had normal CFR. Menopause, hypertension and abnormal stress tests were significantly more prevalent, adiponectin level was significantly decreased, CRP, insulin resistance, and EFT were significantly increased in women with microvascular dysfunction as compared with those without. On multivariate regression analysis EFT emerged as the only independent predictor of microvascular dysfunction (P<0.0001). EFT of >0.45 cm had 85% sensitivity and 75% specificity to detect CFR <2 (P<0.0001). Traditional risk factors for atherosclerosis did not predict women with abnormal microvascular function. CONCLUSIONS EFT has the potential to be an additional and easy diagnostic tool for risk stratification of women with chest pain and angiographically normal coronary arteries.

Quinolones in treatment of human brucellosis: comparative trial of ofloxacin-rifampin versus doxycycline-rifampin.

Quinolones have been reported to be active against Brucella species in vitro. In this prospective randomized study, the efficacy and safety of the combination of ofloxacin plus rifampin were compared with the efficacy and safety of doxycycline plus rifampin, both combinations administered for a 6-week period in treatment of brucellosis. Sixty-one patients were enrolled in the study, and 49 had blood or bone marrow cultures positive for Brucella melitensis. Thirty patients received 200 mg of doxycycline plus 600 mg of rifampin once daily, and 31 patients were treated with 400 mg of ofloxacin plus 600 mg of rifampin once daily for 6 weeks. Nine patients in each group had complications of the disease. There was one therapeutic failure in the ofloxacin-rifampin treatment group, and one patient from each group relapsed (3.3% of those in the doxycycline-rifampin treatment group versus 3.2% of those in the ofloxacin-rifampin treatment group). Gastric discomfort was the major side effect observed in 13 patients (43.3%) who received doxycycline plus rifampin, whereas only 2 patients (6.5%) treated with ofloxacin plus rifampin complained of gastric irritation. These results suggest that the combination of ofloxacin plus rifampin administered for 6 weeks is as effective as doxycycline plus rifampin given for the same period, regardless of the presence of complications of the disease.

Evaluation of Coronary Artery Disease by Computed Tomography Angiography in Patients Treated for Childhood Hodgkin's Lymphoma

PURPOSE To detect pathologies in coronary arteries by computed tomography angiography (CTA) in survivors of childhood Hodgkins lymphoma who have been treated with radiotherapy and/or cardiotoxic agents. PATIENTS AND METHODS Patients with HL who have been in remission for at least 2 years after completion of therapy were included. CBC, lipid profile, urine analysis, brain natriuretic peptide, troponin-T, creatinine kinase-myocardial band, ECG, telecardiography, echocardiography, and CTA of the patients were performed. Cardiac vascular abnormalities were noted. Results A total of 119 patients were included in the study. In 19 patients (16%), we found coronary artery abnormalities. There was a significant difference between the patients who received mediastinal radiotherapy and those who did not (P = .02). By multivariate analysis, in patients receiving mediastinal radiotherapy the risk of developing a coronary artery abnormality was found to increase 6.8 times compared with patients who did not receive mediastinal radiotherapy (P = .009). Stent implantation was performed in a 28-year-old patient because of critical stenosis in right coronary. In two patients some irregularities were detected both in CTA and conventional angiography, and they remained in close follow-up. A 22-year-old patient whose CTA showed critical stenosis in his left anterior descending artery refused the conventional angiography. CONCLUSION To our knowledge, this is the first large study using CTA for detection of coronary abnormalities in patients treated for HL in pediatric age group. Coronary CTA is a minimally invasive tool for early diagnosis of coronary artery disease in patients who were treated with mediastinal radiotherapy and/or cardiotoxic chemotherapy.

Infectious complications of rituximab in patients with lymphoma during maintenance therapy: a systematic review and meta-analysis.

Rituximab maintenance therapy has emerged as an effective treatment for low-grade lymphomas. No major acute or cumulative toxicities were observed in patients receiving rituximab maintenance therapy compared with observation arms in clinical trials. However, B-cells are completely depleted throughout the maintenance period and even longer, which may render patients at high risk for infections. Several infections related to rituximab have been reported in the literature. Yet it is not clear whether rituximab maintenance therapy increases the infectious complications or not. To further investigate this topic, we have performed a systematic review and meta-analysis of randomised controlled trials (RCT). The meta-analysis of five RCTs showed that rituximab maintenance therapy significantly increased the relative risk of both infection and neutropenia in patients with lymphoma. On the basis of the available evidence, patients who received rituximab maintenance treatment have higher risk of neutropenia and infection than those who did not. Previously treated patients particularly with fludarabine containing regimens are more susceptible to infectious complications and require extended vigilance.

Sucralfate in the prevention of radiation-induced oral mucositis.

Radiotherapy-induced mucositis decreases the quality of life by impairing eating, swallowing, and talking and by disturbing sleep. Mucositis may also predispose to local and systemic infections and may cause interruption of radiotherapy course. We studied the efficacy of sucralfate suspension in the prevention and management of oral mucositis and pain during radiotherapy in a double-blind, placebo-controlled, randomized, prospective trial. Twenty-eight patients with head and neck cancer were included in the study. The patients were randomized to use either sucralfate mouth washing (n = 18) or placebo washing (n = 10) during irradiation. Oral mucositis and symptoms were assessed by the same physician using Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring criteria. All patients developed varying degrees of radiation-induced mucositis. Grade 4 mucositis was not encountered in any patient. One patient had grade 1, seven patients grade 2, and two patients grade 3 mucositis in placebo group. In sucralfate group, nine patients each had grade 1 and grade 2 with no grade 3 mucositis. Patients in the sucralfate group experienced significantly lower degree of mucositis than placebo group (p < 0.05). Sucralfate mouth washing is beneficial in decreasing the intensity of radiation-induced mucositis and oral discomfort. It is cheap, easy to administer with no serious side effect, and may be routinely used in patients receiving head and neck radiotherapy.

Wwox and Ap2γ Expression Levels Predict Tamoxifen Response

Purpose: Assessment of expression levels of Wwox, Wwox-interacting proteins Ap2α, Ap2γ, and ErbB4, the Ap2γ transcriptional target protein Her2, and the possible Ap2α transcriptional target PrkaRIα, in breast cancers, to determine their roles in tamoxifen resistance. The hypothesis was that sequestration of Wwox interactors in the cytoplasm might control tamoxifen response. Experimental Design: Tissue sections from 51 tamoxifen-sensitive and 38 tamoxifen-resistant, estrogen receptor α–positive breast cancers were stained for the above proteins, as well as progesterone receptor (PR). The relation of tamoxifen resistance and other clinical features, with level of expression of these proteins, and pairwise correlations among various immunohistochemical markers were determined. Results: Menopausal status, tumor, node, and stage, loss of PR, lost or reduced expression of Wwox, and high level of expression of PrkaRIα, Ap2γ, and Her2 were significantly correlated with tamoxifen resistance. In multivariate analysis, Wwox, PrkaRIα, Ap2γ, and ErbB4 were found to be independent markers of tamoxifen resistance. Reduced Wwox expression was better than PR in prediction of resistance, especially in high-risk patients, and nuclear Ap2γ expression was better than Her2, especially in low-risk patients. Conclusion: The results illustrate the complex relationships among the marker proteins assessed in this in vivo study and suggest new markers for prediction of response to tamoxifen treatment as well as possible new targets for treatment of breast cancer. Wwox and Ap2γ emerge as new biomarkers that may be superior to PR and Her2 in predicting tamoxifen response.

Wnt10b induces chemotaxis of osteosarcoma and correlates with reduced survival.

Osteosarcoma (OS) is a primary malignant tumor of the bone that typically presents in the second decade of life and has a poor prognosis, especially in metastatic cases. Wnt signaling contributes to the pathogenesis of tumors such as colon cancer and malignant melanoma. Wnt signaling controls normal bone formation during embryogenesis and homeostasis in adult organisms, thus we evaluated Wnt signaling in OS.

Detection of Subclinical Cardiac Involvement in Systemic Sclerosis by Echocardiographic Strain Imaging

Background: Cardiac involvement is one of the major problems in systemic sclerosis (SSc). Subclinical cardiac involvement has a higher frequency than thought previously. In this study we investigated whether subclinical cardiac involvement can be detected by using echocardiographic strain imaging in SSc patients without pulmonary hypertension. Methods: Echocardiographic examinations were performed to 27 SSc patients and 26 healthy controls. Left ventricular strain parameters were obtained from apical views and average strain value was calculated from these measurements. Results: There were no significant differences between patients and controls regarding two‐dimensional (2D), conventional Doppler and tissue Doppler velocity measurements. Strain was reduced in 6 of 12 segments of the left ventricle (LV) and in 1 of 2 segments of the right ventricle (RV). Strain rate (SR) was reduced in 2 of 12 segments of the LV and 1 of 2 segments of the RV in SSc patients as compared to controls (P < 0.05 for all). These involvements did not match any particular coronary artery distribution. More important differences were detected by average strain and SR values of the LV between patients and controls (19.78 ± 3.00% vs 23.41 ± 2.73%, P < 0.001; 2.01 ± 0.41 vs 2.23 ± 0.27/sec, P = 0.026, respectively). Furthermore, carbon monoxide diffusion capacity (DLCO) in scleroderma patients significantly correlated with LV average strain (r = 0.59; P = 0.001). Conclusion: Evaluation of ventricular function by using echocardiographic strain imaging appears to be useful to detect subclinical cardiac involvement in SSc patients with normal standard echocardiographic and tissue Doppler velocity findings.

The effect on neuromuscular stability, performance, multi-joint coordination and proprioception of barefoot, taping or preventative bracing

OBJECTIVE The objective of this study was to assess the effects of taping and preventive bracing on functional balance, jumping performance, multi-joint coordination and proprioception on comparison to barefoot and each other. DESIGN Controlled trial as an experiment with the independent variable testing in 3 trials: control (barefooted), preventive bracing, and taping. SETTING The sports physiotherapy research laboratory. PARTICIPANTS Twenty physically active male university students aged between 20 and 28 who had been free from lower extremity pathology for 12 months and had no previous history of ankle sprain served as participants. MAIN OUTCOME MEASURES Single leg balance (s), jumping performance (cm), coordination and proprioception assessments by the Functional Squat System. The software automatically calculated the absolute average error (cm) and the standard deviation (SD) of the average error. Average errors were independently quantified as a function of the action mode (concentric versus eccentric) and of the lower limb (dominant versus non-dominant). RESULTS There was no significant difference among the groups for balance tests (p>0.05). For vertical jump performance of bilateral and the dominant leg there were significant differences that the barefoot group had better results compared to the other groups (p=0.059; 0.017). According to the coordination results of Functional Squat System participants were better in brace and tape situations since the deviations were less for all concentric and eccentric positions. Deviation results for the proprioception test were different for first visual and non-visual deviations for dominant leg (p<0.05). CONCLUSION In conclusion, bracing and taping may play an important role in preventing injury or rehabilitation of the injured ankle by improving concentric and eccentric coordination, proprioception with the ability of reproducing motion in closed kinetic chain while decreasing vertical jump performance. No superiority of brace over tape or vice versa was found in this study.