Intra and peritumoral PET radiomics analysis to predict the pathological response in breast cancer patients receiving neoadjuvant chemotherapy.

OBJECTIVE: The aim of our study was to evaluate the contribution of 18Fluorine-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) radiomic data obtained from both the tumoral and peritumoral area in predicting pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). METHODS: Female patients with a diagnosis of invasive ductal carcinoma who received NAC were evaluated retrospectively. The volume of interest (VOI) of the primary tumor (VOI-T) was manually segmented, then a voxel-thick VOI was added around VOI-T to define the peritumoral area (VOI-PT). Morphological, intensity-based, histogram and texture parameters were obtained from VOIs. The patients were divided into two groups as pCR and non-complete pathological response (npCR). A "radiomic model" was created with only radiomic features, and a "patho-radiomic model" was created using radiomic features and immunohistochemical data. RESULTS: Of the 66 patients included in the study, 21 were in the pCR group. The only statistically significant feature from the primary tumor among patients with pCR and npCR was Morphological_Compacity-T (AUC: 0.666). Between response groups, a significant difference was detected in 2 morphological, 1 intensity, 4 texture features from VOI-PT; no correlation was found between Morphological_Compacity-PT and NGTDM_contrast-PT. The obtained radiomic model's sensitivity and accuracy values were calculated as 61.9% and 75.8%, respectively (AUC: 0.786). When HER2 status was added, sensitivity and accuracy values of the patho-radiomic model increased to 85.7% and 81.8%, respectively (AUC: 0.903). CONCLUSIONS: Evaluation of PET peritumoral radiomic features together with the primary tumor, rather than just the primary tumor, provides a better prediction of the pCR to NAC in patients with breast cancer.

A different perspective on PET/CT before treatment in patients with Hodgkin lymphoma: importance of volumetric and dissemination parameters.

The aim of this study is to investigate the role of the combination of volumetric and dissemination parameters obtained from pretreatment 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting the interim response and progression status in patients with Hodgkin lymphoma (HL). Pretreatment PET/CT images of HL patients were analyzed with LIFEx software, and volumes of interest (VOIs) were drawn with a fixed SUV 4.0 threshold. MTV, SUVmax, and TLG values were obtained from each VOI. Total MTV (tMTV) was calculated by summing the MTV values in all VOIs, and similarly, total TLG (tTLG) was obtained by summing the TLG values. The distance between the centers of the lesions was noted as Dmax, and the distance between the outermost voxels of the lesions as DmaxVox. tMTV/DmaxVox was calculated by dividing the tMTV value by the DmaxVox value, and tTLG/DmaxVox was calculated by dividing the tTLG value by the DmaxVox value. The correlation of pretreatment PET parameters with response groups (complete/poor) and relapse/progression status (stable/progressive) was statistically evaluated. A total of 52 patients were included in the study. Bulky disease, tMTV, tTLG, and tMTV/DmaxVox values were found to be significantly higher in the poor response group. tMTV > 190.60 ml was found to be the only prognostic factor predicting interim PET response. The tMTV/DmaxVox and tTLG/DmaxVox showed statistically significant differences between the groups with and without progression. tMTV/DmaxVox > 7.70 was found to be the only prognostic factor in predicting relapse/progression. The evaluation of tumor burden and dissemination together in 18F-FDG PET/CT before treatment in patients with HL can help us to predict the results of the patients.

Intrathyroidal Parathyroid Adenomas in Primary Hyperparathyroidism: Clinical and Imaging Findings.

Objectives: Primary hyperparathyroidism (PHPT) is a common endocrine disease. Ectopic adenomas may cause a failed surgery which results in persistence or recurrence. Intrathyroidal parathyroid adenoma (ITPA) is a rare reason for PHPT and site of ectopia. Herein, we aimed to investigate the clinical and imaging features of patients with ITPAs and the effectiveness of radiological tools for localization at a tertiary reference center. Methods: The files of 708 consecutive patients who underwent parathyroidectomy for PHPT in our department between January 2007 and December 2021 were investigated retrospectively. PHPT patients with ITPA were included in the study. Patients with missing data were excluded from the study. Clinicopathological features of the patients and radiological evaluation findings were investigated. Results: Twenty-eight (28/708: 3.9%) patients were included in the study. The complete intrathyroidal gland and subcapsular parathyroid gland were observed in 8 (1.1%) and 20 (2.8%) patients, respectively. The ultrasound and parathyroid scintigraphy revealed the accurate localization of ITPA in 25 (89.3%) and 18 (64.3%) patients, respectively. Additional imaging modalities were applied for 10 patients in which conventional localization studies were discordant or inconclusive. ITPAs were most commonly found in the lower gland (n=20) localization. All patients had a successful parathyroidectomy and neither persistence nor recurrence was occurred in the study group. Conclusion: The ITPAs are rare in PHPT. The ultrasound has a high diagnostic rate in experienced hands. The second-line imaging methods may be favorable in the presence of negative or discordant scans. The pre-operative localization studies can detect the ITPAs in most patients, so blind thyroidectomy should be avoided.

Predicting pathological response and overall survival in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy: the role of PET/computed tomography.

BACKGROUND: Gastric cancer is the second leading cause of cancer-related deaths, with a 5-year survival rate of about 20-25%. The ability to predict pathological response (PR) to neoadjuvant chemotherapy (NACT); hence, overall survival (OS) probability of patients can allow the clinician to individualize treatment strategies. We investigated the role of F-18 fluorodeoxyglucose PET-computed tomography (F-18 FDG PET/CT) in predicting histopathologic response and prognosis in locally advanced gastric cancer (LAGC) patients undergoing NACT. METHODS: F-18FDG PET/CT images taken before and after NACT, adenocarcinoma histopathology and operation pyesis reports of 43 LAGC patients were analyzed. Maximum (SUVmax) and mean (SUVmean) standardized uptake values, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of lesions were measured before and after NACT. Changes in percentage were calculated for ΔSUVmax%, ΔSUVmean%, ΔMTV%, ΔTLG%, and cutoff values were determined by receiver operating characteristic curve analysis. NACT response in pathology pyesis was determined according to the College of American Pathologists classification. PR and OS were analyzed with Kaplan-Meier and Cox proportional hazards regression models based on cutoffs found with PET measurements. RESULTS: Cutoffs were ΔSUVmax = 33.31%, ΔSUVmean = 42.96%, ΔMTV = 30.38%, and ΔTLG = 28.14%, and all patients showed significance in PR and OS based on these cutoffs (all P < 0.01). PET/CT findings before and after NACT (ΔMTV > 30.38%, ΔTLG > 28.14%) predicted PR with 100% sensitivity and specificity. Multivariate analysis showed ΔSUVmean as an independent risk factor predicting OS (hazard ratio 0.348, 95% confidence interval 2.91-22.3, P = 0.03). CONCLUSIONS: Metabolic parameters obtained with F-18 FDG PET/CT scanning before and after NACT in LAGC patients can accurately predict PR and OS.

Comparison of the volumetric and radiomics findings of 18F-FDG PET/CT images with immunohistochemical prognostic factors in local/locally advanced breast cancer.

OBJECTIVE: The aim of this study was to determine the change in volumetric and radiomics parameters of fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) imaging in local/locally advanced cancer patients according to immunohistochemical findings. PATIENTS AND METHODS: A total of 72 patients who were diagnosed with local/locally advanced breast cancer and then examined by F-FDG PET/CT for staging were included in this study. Immunohistochemical prognostic factors [estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2), p53 mutation, Ki-67 proliferation index] and histological grades were determined. Standardized uptake value (SUV)-based, volume-based, and radiomics findings were obtained from F-FDG PET/CT images. RESULTS: In cases of ER and PR negativity, Her-2 positivity, presence of the p53 mutation, and Ki-67 index of at least 20% patients, total volumetric parameters were significantly higher in paired comparisons. The results of the ER-negative group were significantly higher than those of ER-positive patients in GLRLM_GLNU, GLRLM_RLNU, GLZLM_GLNU, and GLZLM_ZLNU comparisons. In grade 3 patients, mean SUV, maximum SUV, and GLRLM_LRHGE values were higher than those of grade 2 patients. SUV and volumetric parameters were significantly higher in patients with Ki-67 index of at least 20% than those with less than 20%. Maximum SUV, breast tumor lesion glycolysis values, and entropy in nuclear polymorphism in the 3+ patient group were found to be higher compared with the 2+ patient group. Moreover, patients with mitosis 3+ had significantly higher breast metabolic tumor volume, breast tumor lesion glycolysis, and kurtosis values than the 1+ group. CONCLUSION: ER negativity, triple negativity, high tumor grade, and high nuclear polymorphism were associated with tumor heterogeneity. With respect to ER negativity, PR negativity, high tumor grade, high mitosis number, high Ki-67 index, Her-2 positivity, and the presence of p53 mutation, an increased tumor load were observed. In addition to immunohistochemical parameters, the use of radiomics data is believed to contribute to breast cancer management.

Diagnostic importance of 18F-FDG PET/CT parameters and total lesion glycolysis in differentiating between benign and malignant adrenal lesions.

PURPOSE: Benign adrenal lesions are prevalent in oncologic imaging and make metastatic disease diagnoses difficult. This study evaluates the diagnostic importance of metabolic, volumetric, and metabolovolumetric parameters measured by fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in differentiating between benign and malignant adrenal lesions in cancer patients. PATIENTS AND METHODS: In this retrospective study, we evaluated F-FDG PET/CT parameters of adrenal lesions of follow-up cancer patients referred to our clinic between January 2012 and November 2016. The diagnosis of adrenal malignant lesions was made on the basis of interval growth or reduction after chemotherapy. Patient demographics, analysis of metabolic parameters such as maximum standard uptake value (SUVmax), tumor SUVmax/liver SUVmean ratio (T/LR), morphologic parameters such as size, Hounsfield Units, and computed tomography (CT) volume, and metabolovolumetric parameters such as metabolic tumor volume and total lesion glycolysis (TLG) of adrenal lesions were calculated. PET/CT parameters were assessed using the Mann-Whitney U-test and receiving operating characteristic analysis. RESULTS: In total, 186 adrenal lesions in 163 cancer patients (108 men/54 women; mean±SD age: 64±10.9 years) were subjected to F-FDG PET/CT for tumor evaluation. SUVmax values (mean±SD) were 2.8±0.8 and 10.6±6; TLG were 10.8±9.2 and 124.4±347.9; and T/LR were 1±0.3 and 4.1±2.6 in benign and malignant adrenal lesions, respectively. On the basis of the area under the curve, adrenal lesion SUVmax and T/LR had similar highest diagnostic performance for predicting malignant lesions (area under the curve: 0.993 and 0.991, respectively, P<0.001). Multivariate logistic regression analysis showed that T/LR, adrenal lesion SUVmax, and Hounsfield Units were independent predictive factors for malignancy rather than TLG. CONCLUSION: Irrespective of whether TLG was statistically highly significant for differentiating benign from malignant adrenal lesions, it did not reach the expected performance with a low negative predictive value. This may be because of the malignant but small and benign but large lesions on metabolovolumetric calculation.

The Diagnostic Value of the Correlation between Serum Anti-p53 Antibody and Positron Emission Tomography Parameters in Lung Cancer.

OBJECTIVE: Mutations in the p53 gene are the most commonly observed genetic abnormalities in malignancies. The purpose of this study was to assess the diagnostic value of serum anti-p53 antibody (Ab) along with the correlation between serum anti-p53 Ab level and quantitative positron emission tomography (PET) parameters such as maximum standardized uptake value (SUVmax), SUVave, metabolic tumor volume, total lesion glycolysis (TLG) and tumor size. METHODS: Serum anti-p53 Ab level was studied in three groups. Patients who underwent 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging for staging of previously diagnosed lung cancer constituted the first group, while patients who underwent 18F-FDG PET/CT imaging for evaluation of suspicious pulmonary nodules detected on thorax CT and did not show pathologic FDG accumulation (NAPN=pulmonary nodule with non avid-FDG) were enrolled in the second group. The third group consisted of healthy volunteers. RESULTS: Twenty-eight patients with lung cancer (median age: 62.5, range: 39-77years), 28 patients with NAPN (median age: 65, range: 33-79 years), and 24 healthy volunteers (median age: 62, range: 44-74 years) were enrolled in the study. The serum anti-p53 Ab level was low in healthy volunteers while it was higher in both lung cancer patients and NAPN patients (p<0.05). When serum anti-p53 Ab level and PET parameters were evaluated, there was no significant correlation between serum anti-p53 Ab level and SUVmax, SUVave, TLG, tumor volume and tumor size of patients with lung cancer (p>0.05). Besides, there was no significant difference between serum anti-p53 Ab level and lesion size of NAPN patients (p>0.05). CONCLUSION: It was determined that serum anti-p53 Ab levels are not significantly correlated with PET parameters, and that serum anti-p53 Ab levels increase in any benign or malignant lung parenchyma pathology as compared to healthy volunteers. These results indicate that this Ab cannot be used as a predictor of malignancy in a lung lesion.

Morphologic and Metabolic Comparison of Treatment Responsiveness with 18Fludeoxyglucose-Positron Emission Tomography/Computed Tomography According to Lung Cancer Type.

OBJECTIVE: The aim of the present study was to evaluate the response to treatment by histopathologic type in patients with lung cancer and under follow-up with 18F-fluoro-2deoxy-glucose-positron emission tomography/computed tomography (18F-FDG PET/CT) imaging by using Response Evaluation Criteria in Solid Tumors (RECIST) and European Organisation for Research and Treatment of Cancer (EORTC) criteria that evaluate morphologic and metabolic parameters. METHODS: On two separate (pre- and post-treatment) 18F-FDG PET/CT images, the longest dimension of primary tumor as well as of secondary lesions were measured and sum of these two measurements was recorded as the total dimension in 40 patients. PET parameters such as standardized uptake value (SUVmax), metabolic volume and total lesion glycolysis (TLG) were also recorded for these target lesions on two separate 18F-FDG PET/CT images. The percent (%) change was calculated for all these parameters. Morphologic evaluation was based on RECIST 1.1 and the metabolic evaluation was based on EORTC. RESULTS: When evaluated before and after treatment, in spite of the statistically significant change (p<0.05) in SUVmax, the change was not significant in TLG, in the longest total size and in the longest size (p>0.05). In histopathologic typing, when we compare the post-treatment phase change with the treatment responses of RECIST 1.1 and EORTC criteria; for RECIST 1.1 in squamous cell lung cancer group, progression was observed in sixteen patients (57%), stability in seven patients (25%), partial response in five patients (18%); and for EORTC progression was detected in four patients (14%), stability in thirteen patients (47%), partial response in eleven patients (39%), in 12 of these patients an increase in stage (43%), in 4 of them a decrease in stage (14%), and in 12 of them stability in stage (43%) were determined. But in adenocancer patients (n=7), for RECIST 1.1, progression was determined in four patients (57%), stability in two patients (29%), partial response in one patient (14%); for EORTC, progression in one patient (14%), stability in four patients (57%), partial response in two patients (29%) were observed and in these patients, an increase in stage was detected in 3 of them (43%), while 4 of them remained stable. According to histopathologic diagnosis, between squamous cell cancer and adenocancer cases, no significant difference was determined in terms of SUVmax (p>0.05). Post-treatment SUVmax was significantly different in primary tumor but was not significantly different in nodal involvement and metastatic lesions for squamous cell carcinoma patients as compared to the pre-treatment SUVmax measurements. Similarly, there was no significant difference between primary tumor and nodal involvement for adenocarcinoma patients. CONCLUSION: Whether metabolic or morphologic changes are more accurate in evaluating treatment response in lung cancer remains unknown, and there is no gold standard diagnostic method on this issue yet. The most reliable results can only be achieved by survival curve parameters. However, we believe SUVmax seems to provide more easy and practical data for the evaluation of treatment response.

Is Very High Thyroid Stimulating Hormone Level Required in Differentiated Thyroid Cancer for Ablation Success?

OBJECTIVE: Remnant ablation with radioactive iodine (I-131) is a successful form of treatment that aims to destroy the remaining residual tissue and/or metastatic tissue after total thyroidectomy in differentiated thyroid cancer (DTC) patients. High level of thyroid stimulating hormone (TSH) (≥30 mIU/L) is recommended for success of ablation treatment. In this retrospective study, our aim was to investigate whether the TSH levels at the time of ablation effect the success of radioactive iodine remnant ablation. METHODS: Patients who were diagnosed with DTC, treated with bilateral total/near total thyroidectomy and who were referred for I-131 remnant ablation were included in this study. Patients with undetectable TSH-stimulated serum thyroglobulin (Tg) level, normal physical examination, negative results on whole body scan with I-131, and no evidence of neck lymph node metastasis on ultrasound were defined as disease-free. The correlation between TSH level at the time of ablation and ablation success was assessed. RESULTS: Two hundred sixty one consecutive patients were included in the present study. Mean TSH level was 19.47±6 mIU/L in the 34 patients with TSH <30 mIU/L, while mean TSH level was 73.65±27 mIU/L in the 227 patients with TSH ≥30 mIU/L during I-131 remnant ablation. Ablation was unsuccessful in only one patient with TSH <30 mIU/L who had lung metastasis. Ablation was unsuccessful in 5.1% of patients with TSH ≥30 mIU/L. The effect of TSH level was not significant on ablation success (p=0.472). CONCLUSION: In conclusion, we think that a high TSH serum level alone is not a factor for the success of ablation. Age, presence of metastasis, extent of residual thyroid mass should also be considered. Especially, in the presence of metastatic tissue, obtaining adequate increase in TSH level is not always possible. The success of ablation at lower levels of TSH elevations may be sufficient for patients, and long-term hypothyroidism may not be required.

Potential impact of atelectasis and primary tumor glycolysis on F-18 FDG PET/CT on survival in lung cancer patients.

BACKGROUND: Atelectasis is an important prognostic factor that can cause pleuritic chest pain, coughing or dyspnea, and even may be a cause of death. In this study, we aimed to investigate the potential impact of atelectasis and PET parameters on survival and the relation between atelectasis and PET parameters. MATERIALS AND METHODS: The study consisted of patients with lung cancer with or without atelectasis who underwent (18)F-FDG PET/CT examination before receiving any treatment. (18)F-FDG PET/CT derived parameters including tumor size, SUVmax, SUVmean, MTV, total lesion glycosis (TLG), SUV mean of atelectasis area, atelectasis volume, and histological and TNM stage were considered as potential prognostic factors for overall survival. RESULTS: Fifty consecutive lung cancer patients (22 patients with atelectasis and 28 patients without atelectasis, median age of 65 years) were evaluated in the present study. There was no relationship between tumor size and presence or absence of atelectasis, nor between presence/absence of atelectasis and TLG of primary tumors. The overall one-year survival rate was 83% and median survival was 20 months (n=22) in the presence of atelectasis; the overall one-year survival rate was 65.7% (n=28) and median survival was 16 months (p=0.138) in the absence of atelectasis. With respect to PFS; the one-year survival rate of AT+ patients was 81.8% and median survival was 19 months; the one-year survival rate of AT- patients was 64.3% and median survival was 16 months (p=0.159). According to univariate analysis, MTV, TLG and tumor size were significant risk factors for PFS and OS (p<0.05). However, SUVmax was not a significant factor for PFS and OS (p>0.05). CONCLUSIONS: The present study suggested that total lesion glycolysis and metabolic tumor volume were important predictors of survival in lung cancer patients, in contrast to SUVmax. In addition, having a segmental lung atelectasis seems not to be a significant factor on survival.

Importance of postoperative stimulated thyroglobulin level at the time of 131I ablation therapy for differentiated thyroid cancer.

BACKGROUND: Serum thyroglobulin detection plays an essential role during the follow-up of thyroid cancer patients treated with total/near total thyroidectomy and radioiodine ablation. The aim of this retrospective study was to evaluate the relationship between stimulated serum thyroglobulin (Tg) level at the time of high dose 131I ablation and risk of recurrence, using a three-level classification in patients with differentiated thyroid cancer (DTC) according to the ATA guidelines. Also we investigated the relationship between postoperative stimulated Tg at the time of ablation and DxWBS results at 8-10 months thereafter. MATERIALS AND METHODS: Patients with radioiodine accumulation were regarded as scan positive (scan +). If there was no relevant pathological radioiodine accumulation or minimal local accumulation in the thyroid bed region, this were regarded as scan negative (scan-) at the time of DxWBS. We classified patients in 3 groups as low, intermediate and high risk group for assessment of risk of recurrence according to the revised ATA guidelines. Also, we divided patients into 3 groups based on the stimulated serum Tg levels at the time of 131I ablation therapy. Groups 1-3 consisted of patients who had Tg levels of ≤ 2 ng/ml, 2-10 ng/ml, and ≥ 10 ng/ml, respectively. RESULTS: A total of 221 consecutive patients were included. In the high risk group according to the ATA guideline, while 45.5% of demonstrated Scan(+) Tg(+), 27.3% of patients demonstrated Scan(-) Tg(-); in the intermediate group, the figures were 2.3% and 90.0% while in the low risk group, they were 0.6% and 96.4%. In 9 of 11 patients with metastases (81.8%), stimulated serum Tg level at the time of radioiodine ablation therapy was over 10, however in 1 patient (9.1%) it was < 2 ng/mL and in one patient it was 2-10 ng/mL (p = 0.005). Aggressive subtypes of DTC were found in 8 of 221 patients and serum Tg levels were ≤ 2 ng/ml in 4 of these 8. CONCLUSIONS: We conclude that TSH-stimulated serum thyroglobulin level at the time of ablation may not determine risk of recurrence. Therefore, DxWBS should be performed at 8-12 months after ablation therapy.

p53 antibody: is it an indicator of dedifferentiated thyroid cancer?

AIM: Radioiodine is the most effective treatment modality in differentiated thyroid carcinoma, either in metastatic or residual thyroid tissue. However, sometimes dedifferentiation can develop and the effectiveness of radioactive I-131 decreases. The p53 is a tumor suppressor gene which plays an important role in controlling normal cell proliferation regulation. In the serum of healthy individuals, the presence of p53 autoantibodies is extremely rare. Mutations in this gene cause an accumulation of non-functional proteins and may lead to development of anti-p53 antibodies. The aim of the present study was to devise a simple blood test that could lead to early identification of patients with dedifferentiation. In this respect, we investigate whether the serum level of anti-p53 antibody is of diagnostic value in the follow-up of patients with high levels of thyroglobulin (Tg) and negative I-131 scan. MATERIALS AND METHODS: Patients who were diagnosed with thyroid cancer, treated with total or near total thyroidectomy and referred for I-131 therapy or low dose I-131 whole body scan were included in our study. Blood samples were taken before the administration of I-131 orally in the group of patients. Besides, 28 healthy subjects were included. We quantified the presence of p53 autoantibodies from serums. RESULTS: In the present study were enrolled 171 patients with a mean age of 47.7±13.5 years (range 16­80 years) and 28 healthy subjects with an age range of 18­52 years (mean 36.0±9.8 years). One hundred and forty-eight patients had papillary (86.5%), 7 (4.1%) follicular, 10 (5.8%) thyroid tumors of uncertain malignant potential, 2 (1.2%) Hürthle cell carcinoma, 3 (1.8%) poor differentiated, and 1 (0.6%) undifferentiated thyroid carcinoma. The p53 antibodies were positive in 16 (9.4%) patients and negative in 155 (90.6%). The p53 antibodies were positive in 3 (10.7%) healthy subjects, and negative in 25 (89.3%) healthy subjects. In five patients with high Tg level and negative radioiodine scan, who were accepted as dedifferentiated, p53 antibodies were also negative. CONCLUSION: The results of the present study suggested that the level of serum p53 antibody seems to be of limited value in the demonstration of dedifferentiation in thyroid cancer patients.

Investigation of the role of the NO-cGMP pathway on YC-1 and DEA/NO effects on thoracic aorta smooth muscle responses in a rat preeclampsia model.

The present study was designed to investigate the effects of YC-1, a nitric oxide (NO)-independent soluble guanylate cyclase (sGC) activator, and DEA/NO, a NO donor, on smooth muscle responses in the preeclampsia model with suramin-treated rats and on the levels of cyclic guanosine monophosphate (cGMP) of thoracic aorta rings isolated from term-pregnant rats. Rats of 2 groups, control group and suramin group, were given intraperitoneal injection of saline or suramin, respectively. Suramin injection caused increased blood pressure, protein in urine, and fetal growth retardation. Thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction and papaverine relaxation responses were similar. Relaxation responses of YC-1 and DEA/NO decreased in suramin group. In both groups in the presence of ODQ, a sGC inhibitor, the relaxation responses of YC-1 and DEA/NO decreased. The cGMP content was determined by radioimmunoassay technique. The content of cGMP in the suramin group decreased. In the presence of YC-1 and DEA/NO in both groups, cGMP content increased, but in ODQ-added groups, there was a significant decrease. We conclude that in preeclampsia, the decrease of relaxation responses and the decrease of cGMP content could be due to the reduction in stimulation of sGC and the decrease in cGMP levels.

Possible roles of the xenobiotic transporter P-glycoproteins encoded by the MDR1 3435 C>T gene polymorphism in differentiated thyroid cancers.

BACKGROUND: P-glycoprotein (Pgp), encoded by the multidrug resistance 1 (MDR1) gene, is an efflux transporter which plays an important role in pharmacokinetics. The current preliminary study was designed to determine associations between a germ-line polymorphism in the MDR1 gene with differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: In the current case-control study, 60 differentiated thyroid cancers (DTC)- 45 papillary TC (PTC), 9 follicular TC(FTC) and 6 well-differentiated tumors of uncertain malignant potential (WDT-UMP) were examined. Results were compared to a healthy control group (n=58) from the same population. Genomic DNA was extracted from peripheral blood with EDTA and the target gene was genotyped by real-time PCR. RESULTS: Carriers of the variant allele of MDR1 exon 26 polymorphism were at 2.8-fold higher risk of DTC than the control group (odds ratio [OR]: 0.3805, 95% confidence interval [Cl]: 0.1597-0.9065 (p> 0.046). CONCLUSIONS: Presented results suggest that the MDR1 3435TT genotype might influence risk of development of DTC and that the CC genotype might be linked to a poor prognosis. Large-scale studies are now needed to validate this association.

The Evaluation of Microcarcinoma in Differentiated Thyroid Cancers According to Old and New TNM Classification.

OBJECTIVE: In this study, we aimed to evaluate the tumor size for proximal and distant metastases when the new and old TNM classification is taken into account in differentiated thyroid cancers. MATERIAL AND METHODS: Two hundred sixty eight patients diagnosed with thyroid carcinoma, undergoing bilateral total or subtotal thyroidectomy treated with high doses of I-131 were examined retrospectively. The data of these patients were compared after classification, according to tumor size <1 cm and <2 cm, lymph node metastases thyroid and tumor capsule invasion at the time of diagnosis, and accumulation of abnormal activity in post I-131 treatment whole-body scan. I-131 uptakes besides physiological and thyroid bed were considered as abnormal activity uptakes. RESULTS: A total of 268 patients with average age of 19-82 yrs (mean: 47.0±13.8 yrs) were included in the study. At postoperative histopathological evaluation, 228 (85.1%) of patients were reported as papillary, 13 (4.9%) as follicular, 23 (8.6%) as well differentiated tumor of unknown malignant potential, 2 (0.7%) as insular and 2 (0.7%) as Hürthle-cell carcinoma. In patients with known tumor size, 96 of 207 (46.4%) patients' tumor size was <1 cm and in 111 (53.6%) >1 cm. In the same group, according to the revised TNM classification, in 149 of 207 patients (72%) the tumor size was <2 cm, whereas in 58 (28%) >2 cm. Of 187 patients with negative lymph nodes, 15 (8%) showed abnormal activity accumulation in the first post I-131 treatment whole-body scan and 10 (40% of 25 patients) positive lymph node (p<0.05) involvement. CONCLUSION: Since the treatment of patients with microcarcinoma is controversial, tumor size should not be the only factor considered in patients with differentiated thyroid cancer Tissue tumor invasion, age, gender and multifocality should also be taken into account. CONFLICT OF INTEREST: None declared.

Evaluation of myocardial viability with thallium-201 infusion MPSPECT after oral glucose application in patients with chronic coronary artery disease.

AIM: The aim of this study was to evaluate the myocardial viability in nondiabetic patients with chronic coronary artery disease (CCAD) or past myocardial infarction (MI), using thallium-201 infusion myocardial perfusion single-photon emission computed tomography (MPSPECT) imaging after oral glucose application (Glu+Tl-infusion). MATERIALS AND METHODS: In this study, 33 nondiabetic patients (three female, 30 male, mean age: 55.24+/-11 years, range: 33-77 years) with MI history or known CCAD were included. Rest/redistribution/24 h-late-MPSPECT imaging was performed for all patients. In all patients in whom fixed perfusion defect was observed on any wall of the left ventriculi, after 24 h-late-MPSPECT imaging, 75 g oral glucose was given. Thirty minutes later, 1 mCi thallium-201 in 100 ml of physiological saline solution was applied in a period of 20 min by slow infusion. After infusion at the 10th minute, MPSPECT imaging was performed. Perfusion was evaluated visually for a total of 3432 segments with the 26-segment 5-point scoring technique. Scoring measured perfusion as 0 = no perfusion defect, 1 = mildly reduced, 2 = moderately reduced, 3 = severely reduced, and 4 = absent uptake. Scores '0 and 1' were considered normal and scores '2-4' were considered abnormal. RESULTS: For serum insulin levels measured after glucose application, a significant increase was determined, according to the period before glucose application (P<0.001). When compared with rest MPSPECT images, segmental perfusion improvement both in redistribution and in the 24 h-late-MPSPECT images were 16.3 and 18.3%, respectively. This ratio was found to be 27.2% for Glu+Tl-infusion images. The ratios of segments in which perfusion was worsening were calculated to be 9.4, 14.5, and 7.3%, respectively, for redistribution, 24 h-late-MPSPECT, and Glu+Tl-infusion images. When this evaluation was made for all three vessel areas, again the highest perfusion improvement and the lowest perfusion worsening were detected for Glu+Tl-infusion images. In addition, when this evaluation was made for the three vessel areas according to the coronary narrowing degree, again the highest perfusion improvement was detected for Glu+Tl-infusion images, in segments in the left anterior descending artery, and right coronary artery areas with >/=90% narrowing. In rest images, in segments with segmental scores of 3 and 4, when the total reversibility ratio was evaluated, this ratio was calculated to be 0.7% for redistribution images and 4.5% for 24 h-late-MPSPECT. The highest total reversibility ratio in these segments was detected with Glu+Tl-infusion images to be 10.3%. When we evaluated the patients with respect to the MI history time, the highest segmental perfusion improvement was detected in patients with 0-3 months of MI history. CONCLUSION: We conclude that in nondiabetic patients who are known to have CCAD or past MI history, Glu+Tl-infusion is an easily applicable method that gives better results for the evaluation of myocardial viability.

Leptin and bone mineral density in haemodialysis patients.

INTRODUCTION: There are very few data about relations between leptin and bone mineral density (BMD) in regular haemodialysed patients. We aimed to examine the relationship of serum leptin levels with BMD values in dialysed patients. We also assessed whether leptin is a significant predictor of BMD in haemodialysed patients. MATERIALS AND METHODS: Leptin levels were studied using commercially available kits and BMD values were calculated using dual energy X-ray absorptiometry (DEXA) at femoral neck and distal radius in 74 (30 men and 44 women ) haemodialysis patients. RESULTS: BMD values at the femoral neck and distal radius did not differ significantly between the 2 genders. BMD at the distal radius correlated positively with bone alkaline phosphatase (BAP) (r = 0.503, P = 0.005) in male patients and correlated positively with phosphorus (r = 0.343, P = 0.02) in female patients. The time ondialysis treatment was longer in men (59 +/- 48 vs 44 +/- 41) but the difference was not statistically significant. Leptin levels were negatively correlated with BMD at the distal radius (r = -0.250 and P = 0.03) in all patients. Serum leptin levels were also correlated with body mass index (BMI) in all the patients (r = 0.749 and P = 0.001) and in both genders (r = 0.653 and P = 0.001 in women, r = 0.704 and P = 0.001 in men). In multivariate regression analysis, it was found that leptin level was not an independent determinant of BMD at all skeleton sites measured. CONCLUSIONS: There was significant difference between the 2 genders with reference to leptin levels, BMI, phosphorus and creatinine. Serum leptin levels are not significant predictors of BMD in the current study.

The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model.

The pathophysiology of pre-eclampsia is still unknown thus effective primary prevention is not possible at the stage. The present study was conducted to research the smooth muscle responses in the pre-eclampsia model with suramin treated rats and the effect of phosphodiesterase-5 (PDE5) inhibitor on these responses. Rats of three groups; control, suramin and suramin+sildenafil were given intraperitoneal injections of saline, suramin or sildenafil citrate. Suramin injections caused increased blood pressure, protein in urine and caused fetal growth retardation. The use of sildenafil citrate straightened significantly both blood pressure and average fetus weight, but did not reach to control values. At the end of pregnancy, thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction responses, sodium nitroprusside and papaverine relaxation responses were similar in three groups. Contraction responses of phenylephrine, increased significantly in suramin group. Relaxation responses of acethylcholine and bradykinin decreased in suramin group. The use of sildenafil citrate partially straightened both relaxation and contraction responses, but did not reach to control values. In all groups in the presence of L-nitromonomethylarginine (L-NAME), 1H-(1, 2, 4) oxadiazole (4, 3-a) guinoxalin-1-one (ODQ) and indomethacin decreased the relaxation responses of acetylcholine and bradykinin. The cyclic guanosine monophosphate (cGMP) content of thoracic aorta tissue was determined by radioimmunoassay technique. The content of cGMP in suramin group decreased and use of sildenafil citrate increased the cGMP content but did not reach to control values. We conclude that in pre-eclampsia, the increase of contraction responses, the decrease of relaxation responses and the decrease of cGMP content can depend on insufficiency about synthesis or release of relaxant factors which was released from the vessel endothelium. The results in this study show that in pre-eclampsia; PDE5 inhibitors enhance endothelial function and may be used for protection. Further studies are needed to clear the efficiency and safety of PDE5 inhibitors.

Validity of the CA125 level in the differential diagnosis of pulmonary tuberculosis.

The aim of the current study was to determine the possible crucial role of cancer antigen 125 (CA125) in the diagnosis of pulmonary tuberculosis (PTB). The CA125 levels of study and control groups were statistically compared. In a total of 146 patients that were included in the current study, 30 had active PTB, 37 inactive PTB, 28 community-acquired pneumonia (CAP), 25 pleural or pulmonary malignancies, and 13 patients exacerbation of chronic obstructive pulmonary disease. The mean CA125 levels in PTB, inactive PTB, CAP, and pleural-pulmonary malignancies were 118.46 +/- 248.41, 40.80 +/- 50.95, 47.76 +/- 60.76, and 57.77 +/- 65.59, respectively. For active-inactive discrimination of PTB, with a cut-off level of >35 U/ml, the sensitivity, specificity, positive predictive value, and negative predictive value of CA125 were 63, 59, 56, and 67%, respectively. Increased CA125 levels were detected in active PTB in the current results. The current results also show that high level CA125 should be reconsidered in the prediagnosis and/or discrimination of active and inactive PTB patients.