Zekiye Hasbek

Increased T-Allele Frequency of 677 C>T Polymorphism in the Methylenetetrahydrofolate Reductase Gene in Differentiated Thyroid Carcinoma

BACKGROUND Epigenetic alterations in the global DNA methylation status may be associated with an increased risk of some cancer types in humans. The methylenetetrahydrofolate reductase (MTHFR) gene is involved in folic acid metabolism and plays an essential role in inherited DNA methylation profiles. The common 677 C>T and 1298 A>C polymorphisms in the MTHFR gene cause the production of a thermolabile enzyme with reduced function and, eventually, genomic DNA hypomethylation. The current preliminary study was designed to determine the association between germ-line polymorphism in the MTHFR gene and differentiated thyroid carcinoma (DTC). METHODS In the current case-control study of 60 thyroid carcinomas (TC); 45 papillary TC, 9 follicular TC, and 6 DTC of an uncertain malignant potential were examined. Genomic DNA was extracted from peripheral blood with EDTA, genotyped by a multiplex real-time polymerase chain reaction. RESULTS An elevated 2.33-fold risk was observed for DTC in individuals with the 677TT genotype when compared with the control group (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.03-3.58). Current DTC patients showed similar results as a control group for the 1298 A>C allele. No significant risk was detected for the homozygous 1298CC genotype (CC vs. AA or AC) (OR: 1.30, 95% CI: 0.73-2.29). CONCLUSION The current results are supportive of the hypothesis that the homozygous MTHFR 677TT genotype increases the risk factor of developing thyroid cancer, and further large-scale studies are needed to validate this association.

Survival analysis and prognostic factors for neuroendocrine tumors in Turkey.

BACKGROUND This study aimed to determine the demographical distribution, survival and prognostic factors for neuroendocrine tumors monitored in our clinic. MATERIALS AND METHODS Data for 52 patients who were admitted to Cumhuriyet University Medical Faculty Training Research and Practice Hospital Oncology Center between 2006 and 2012 and were diagnosed and treated for neuroendocrine tumors were investigated. RESULTS Of the total, 30 (58%) were females and 22 (42%) were males. The localization of the disease was gastroenteropancreatic in 29 (56%) patients and other sites in 23 (44%). The most frequently involved organ in the gastroenteropancreatic system was the stomach (n=10, 19%) and the most frequently involved organ in other regions was the lungs (n=10, 19%). No correlation was found between immunohistochemical staining for proteins such as chromogranin A, synaptophysin, and NSE and the grade of the tumor. The patients were followed-up at a median of 24 months (1-90 months). The three-year overall survival rate was 71%: 100% in stage I, 88% in stage II, 80% in stage III, and 40% in stage IV. The three-year survival rate was 78% in tumors localized in the gastroenteropancreatic region, and 54% in tumors localized in other organs. In the univariate analysis, gender, age, performance status of the patients, grade, localization, surgical treatment, and neutrophil/ lymphocyte ratio (≤ 5 versus >5) affected the prognosis of the patients. CONCLUSIONS Most of the tumors were localized in the gastroenteropancreatic region, and the three-year survival rate in tumors localized in this region was better than the tumors localized in other sites. Surgical treatment was a positive independent prognostic factor, whereas Grade 3 and a neutrophil/lymphocyte ratio of >5 were negative independent prognostic factors.

Contrast-induced nephropathy: controlled study by differential GFR measurement in hospitalized patients.

Background Without appropriate control measures, contrast-induced nephropathy (CIN) incidence has been claimed to be overestimated. Purpose To evaluate the relationship and the difference between differential serum creatinine (DsCr), which is currently surrogating as a marker of CIN, and measured differential GFR values as a control measure (DGFR) in hospitalized patients. Material and Methods GFR was measured two times by Tc-99m DTPA, before and 48 h after contrast media (CM), along with sCr and BUN in 35 inpatients (22 men, 13 women, mean age ± SD = 61 ± 14) with no known chronic kidney disease. Results Relationship was moderate between GFR and sCr (R = 0.50, P < 0.01) in the study population. Pre-CM vs. post-CM values of GFR, sCr and BUN were not statistically different as (mean ± SD); 78 ± 36 vs. 73 ± 35 mL/min/1.73m2, 0.95 ± 0.26 vs. 0.94 ± 0.26 mg/dl and 21 ± 16 vs. 19 ± 13 mg/dl, respectively, in the study group. According to basal GFR values, 14 patients (40%) seemed carrying risk of CIN (GFR < 60 mL/min/1.73m2) in whom only two had sCr >1.5 mg/dl. Twenty-five patients (71%) had discordant results in relation to DsCr and DGFR and two of them had CIN according to classical definition of DsCr, although having basal sCr <1.1 mg/dl. Yet, both had low, but stable GFR values. None of patient from the study group underwent hemodialysis. Conclusion Significant discordance was observed between differential serum creatinine and measured differential GFR in hospitalized patients, suggesting that CIN incidence calculations only based on hospital registry may carry risk of error.

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.

The negative prognostic impact of bone metastasis with a tumor mass

OBJECTIVE: Typically, bone metastasis causes osteolytic and osteoblastic lesions resulting from the interactions of tumor cells with osteoclasts and osteoblasts. In addition to these interactions, tumor tissues may grow inside bones and cause mass lesions. In the present study, we aimed to demonstrate the negative impact of a tumor mass in a large cohort of patients with bone metastatic cancer. METHODS: Data from 335 patients with bone metastases were retrospectively reviewed. For the analysis, all patients were divided into three subgroups with respect to the type of bone metastasis: osteolytic, osteoblastic, or mixed. The patients were subsequently categorized as having bone metastasis with or without a tumor mass, and statistically significant differences in median survival and 2-year overall survival were observed between these patients (the median survival and 2-year overall survival were respectively 3 months and 16% in patients with a tumor mass and 11 months and 26% in patients without a tumor mass; p<0.001). RESULTS: According to multivariate analysis, the presence of bone metastasis with a tumor mass was found to be an independent prognostic factor (p=0.011, hazard ratio: 1.62, 95% confidence interval: 1.11–1.76). Bone metastasis with a tumor mass was more strongly associated with osteolytic lesions, other primary diseases (except for primary breast and prostate cancers), and spinal cord compression. CONCLUSION: Bone metastasis with a tumor mass is a strong and independent negative prognostic factor for survival in cancer patients.

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

AimThe 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+201Tl-infusion). Materials and methodsIn 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. ResultsFor 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+201Tl-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+201Tl-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+201Tl-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+201Tl-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+201Tl-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. ConclusionWe conclude that in nondiabetic patients who are known to have CCAD or past MI history, Glu+201Tl-infusion is an easily applicable method that gives better results for the evaluation of myocardial viability.

A large renal pelvic diverticulum, presenting incomplete excretion during tc-99m mag-3 scintigraphy and tracer accumulation on tc-99m dmsa scintigraphy; a case report

This case report illustrates the dynamic and static renal scintigraphic images of a patient with an unusual large diverticulum of the renal pelvis. The initial diagnosis by intravenous pyelography (IVP) and ultrasonographic (US) examination was a renal pelvic diverticulum of the left kidney, and the patient was referred to the nuclear medicine department for exploration of the effect of the pelvic diverticulum on renal functions.We performed dynamic renal scintigraphy with technetium-99m (Tc-99m) labeled mercapto-acetyl triglycine (MAG-3) and static renal scintigraphy with Tc-99m labeled dimercaptosuc-cinic acid (DMSA). In dynamic renal scintigraphy, bilaterally normal concentration function was observed. While right kidney excretion function was normal, an incomplete excretion pattern was seen on the left side. Complete urinary flow obstruction occurred approximately at the 10th minute of the acquisition, which did not seem to respond to the i.v. furosemide application. However, when only the renal cortex was included in the region of interest, the obstructive pattern disappeared. In static renal scintigraphy, a large renal pelvic diverticulum localized antero-medially was clearly visualized in the left-anterior oblique projection, most probably due to accumulation of radiopharmaceutical inside it.This case showed that a renal pelvic diverticulum should be thought of when an incomplete excretion pattern is seen on dynamic renal scintigraphy. Using only a cortical region of interest may also help to distinguish other types of obstructive pattern from diverticulum. Additionally, Tc-99m DMSA scintigraphy may show diverticulum localization with antero-oblique projections in addition to routine projections.

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.

Is sensorineural hearing loss related with thyroid metabolism disorders

Objectives: In this study, we measured hearing thresholds in patients diagnosed with hyperthyroidism or hypothyroidism with high-frequency audiometry and otoacoustic emission before and after treatment to determine whether hearing losses were cochlear or retrocochlear and whether they would improve with medical therapy. Materials and Methods: This study was conducted on patients diagnosed with hyperthyroidism and hypothyroidism at Cumhuriyet University, Faculty of Medicine, Department of Endocrinology and Metabolism and accepting to participate in the study. We measured the hearing thresholds of the study population during the pretreatment period and in posttreatment euthyroid period. Result: The audiometric findings of patients with hyperthyroidism were better than those of the control group especially at high frequencies. Sensorineural hearing loss was detected in the euthyroid period. We compared the audiometric findings of the patients with hypothyroidism and the controls. We found sensorineural hearing loss in patients with hypothyroidism, especially at low frequencies. Conclusions: The results of this study showed that both hyperthyroidism and hypothyroidism may have an effect on hearing pathway disorders. Medical therapy may lead to hearing loss in patients with hyperthyroidism, and the underlying factors should be investigated in detailed future studies. It was shown in our study that the hearing loss induced by hypothyroidism may improve with medical therapy. Therefore, in all patients with thyroid dysfunction, hearing levels should be monitored closely with audiometric tests.

Importance of Postoperative Stimulated Thyroglobulin Level at the Time of 131 I 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.