Özgür Ömür

An update on molecular biology of thyroid cancers.

Differentiated thyroid cancer (DTC) is the most common endocrinological malignancy. There are several histological variants such as papillary and follicular thyroid carcinoma. Many patients with well-differentiated subtypes of DTC are cured by surgery alone or with radioiodine, while poorly differentiated types usually have a worse prognosis. The aggressiveness of thyroid tumors is closely linked to specific gene alterations. Several diagnostic and prognostic molecular markers such as BRAF and RAS point mutations; RET/PTC and PAX8/PPARγ gene rearrangements; MAPK, PI3K, p53, Wnt-beta catenin, HIF1α and NF-kappaB signaling pathways; microRNA profiles and aberrant methylation have been demonstrated in more than 70% of DTC. Diagnostic use of these molecular markers may be optimized for identifying higher risks of mortality, tumor recurrence and metastatic potential. Understanding the molecular biology of thyroid cancers can be an important avenue for diagnosis and treatment of radioiodine-refractory or inoperable DTC patients with novel molecular targeted therapeutic agents.

Relationship between gastric emptying and gastroesophageal reflux in infants and children.

Purpose: The aim of our study was to evaluate the relationship between gastric emptying and gastroesophageal reflux (GER) in infants and children. Methods and Materials: One hundred eight patients (pts) between 3 months and 5 years of age (77 boys, 31 girls) with clinical suspicion of GER disease were included in the study. Patients were divided into 2 groups according to the age range: group A, 0–2 years (57 pts), and group B, 2–5 (51 pts) years. Each group was divided into 2 subgroups according to the scintigraphic study as GER-positive and -negative. Cows milk with Tc-99m sulfur colloid as radiotracer was used. Gastric emptying was expressed as the half emptying time (T1/2). The detection of activity in the esophagus at any time during scintigraphy was considered an indicator of GER episodes. Reflux episodes were graded as grade 1 if activity was detected on one or 2 frames and grade 2 if activity was detected on more than 2 frames. Results: Forty of the 108 patients (37%) had GER findings on scintigraphy. The comparison of gastric emptying time between positive GER scintigraphy and negative GER scintigraphy groups was not statistically significant in any age group. No association was found between age and rate of gastric emptying time. Although the comparison of T1/2 between grade 1 patients and the GER-negative group was not statistically significant, grade 2 patients showed significant differences and had prolonged gastric emptying times. Mild statistical correlation between the number of reflux episodes and gastric emptying half time was found. Conclusions: As a conclusion, the relation between gastroesophageal reflux and delayed gastric emptying cannot be ignored. Our results support delayed gastric emptying to be a pathogenetic factor in gastroesophageal reflux in infants and children.

Clinical implications of diffuse hepatic uptake observed in postablative and post-therapeutic I-131 scans.

Diffuse hepatic uptake of I-131 either on diagnostic or post-therapeutic scans is a usual finding in patients with differentiated thyroid carcinoma. The aim of this study was to evaluate the frequency and clinical significance of diffuse hepatic uptake of radioiodine on post-therapeutic (PT) and postablative (PA) whole-body scans. A total of 720 PA and 172 PT I-131 scans in a total of 732 patients with differentiated thyroid carcinoma were retrospectively reviewed. Residual thyroid tissue and diffuse liver uptake of I-131 were classified from 0 to 4. The correlation between the liver and thyroid remnant uptake score, dose of radioiodine, serum thyroglobuline (Tg), liver function test levels (ALT, AST), liver ultrasonography, presence of metastatic foci, and recurrent disease were examined. Diffuse hepatic uptake was observed in 701 of 722 (94.2%) PA and 162 of 172 (97%) PT whole body I-131 scans. Hepatic radioiodine uptake was positively correlated with the dose of administered I-131 and increased levels of serum AST and ALT. Liver uptake scores of patients with hepatosteatosis were significantly higher than all study groups. However, no evidence of a relationship between diffuse visualization of liver and serum thyroglobulin levels, uptake score of thyroid remnants, presence of local or distant metastatic foci on I-131 scan, and recurrence rate could be demonstrated. The lack of correlation between hepatic radioactive iodine (RAI) uptake and Tg levels, functioning metastatic tissue or thyroid remnants suggests that this finding may be related to factors other than thyroid tissue. The positive correlation between administered RAI dose, hepatic enzymes and hepatosteatosis support the conclusion that diffuse hepatic RAI uptake may be related to different mechanisms as well.

False-positive I-131 accumulation in a hepatic hydatid cyst.

In this report, a case of differentiated thyroid carcinoma having false-positive I-131 accumulation due to a large hydatid cyst in the liver is presented. Abdominal sonographic examination of a 37-year-old patient with differentiated thyroid carcinoma demonstrated an ovoid, complex cystic mass containing cystic parts as well as solid-appearing components in the right lobe of liver, which is concordant with a type CE-3 hydatid cyst. The postablative whole-body scan obtained 10 days after 100 mCi I-131 therapy displayed intense and homogeneous uptake of radioiodine in the liver. Hepatic cystic mass was removed, and postoperative histologic evaluation confirmed hydatid disease. Some cystic lesions of the kidney and liver have been previously reported as causes of false-positive radioiodine accumulation.

Fluorine-18 fluorodeoxyglucose PET-CT for extranodal staging of non-Hodgkin and Hodgkin lymphoma

PURPOSE We aimed to evaluate the role of fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) involving care-dose unenhanced CT to detect extranodal involvement in patients with non-Hodgkin and Hodgkin lymphoma. MATERIALS AND METHODS Lymphoma patients (35 Hodgkin lymphoma, 75 non-Hodgkin lymphoma) who were referred for 18F-FDG PET-CT imaging, following a diagnostic contrast-enhanced CT (CE-CT) performed within the last month, were included in our study. A total of 129 PET-CT images, and all radiologic, clinical, and pathological records of these patients were retrospectively reviewed. RESULTS In total, 137 hypermetabolic extranodal infiltration sites were detected by 18F-FDG PET-CT in 62 of 110 patients. There were no positive findings by CE-CT that reflected organ involvement in 40 of 137 18F-FDG-positive sites. The κ statistics revealed fair agreement between PET-CT and CE-CT for the detection of extranodal involvement (κ=0.60). The organs showing a disagreement between the two modalities were the spleen, bone marrow, bone, and thyroid and prostate glands. In all lesions that were negative at CE-CT, there was a diffuse 18F-FDG uptake pattern in the PET-CT images. The frequency of extranodal involvement was 51% and 58% in Hodgkin and non-Hodgkin lymphoma patients, respectively. There was a high positive correlation between the maximum standardized uptake values of the highest 18F-FDG-accumulating lymph nodes and extranodal sites (r=0.67) in patients with nodal and extranodal involvement. CONCLUSION 18F-FDG PET-CT is a more effective technique than CE-CT for the evaluation of extranodal involvement in Hodgkin and non-Hodgkin lymphoma patients. PET-CT has a significant advantage for the diagnosis of diffusely infiltrating organs without mass lesions or contrast enhancement compared to CE-CT.

Recurrence Incidence in Differentiated Thyroid Cancers and the Importance of Diagnostic Iodine-131 Scintigraphy in Clinical Follow-up.

Objective: Differentiated thyroid cancers (DTC) are tumors with good prognosis. However, local recurrence or distant metastasis can be observed. In our study, we aimed to investigate the incidence of recurrence and the importance of diagnostic iodine-131 whole body scan (WBS) in clinical follow-up in patients with DTC. Methods: The clinical data of 217 patients with DTC who were followed-up more than 3 years were reviewed retrospectively. The incidence of recurrence was investigated in a group of patients who had radioactive iodine (RAI) treatment and showed no sign of residual thyroid tissue or metastasis with diagnostic WBS that was performed at 6-12 months after therapy and had a thyroglobulin (Tg) level lower than 2 ng/dl. Results: At the time of diagnosis, ten cases had thyroid capsule invasion, 25 cases had extra-thyroid soft tissue invasion, 11 patients showed lymph node metastasis and four patients had distant organ metastasis. One hundred forty-five patients had RAI treatment at ablation dose (75-100 mCi), whereas 35 patients had RAI treatment at metastasis dose (150-200 mCi). Thirty-seven patients with papillary microcarcinoma did not receive RAI treatment. In 12 (%7.5) of the 160 patients who were considered as “successful ablation”, a recurrence was identified. Recurrence was detected by diagnostic WBS in all cases and stimulated Tg level was <2 ng/dL with the exception of the two cases who had distant metastasis. Conclusion: Identification of pathological findings with WBS in patients who developed local recurrence in the absence of elevated Tg highlights the importance of diagnostic WBS in clinical follow-up.

18F-FDG and 18F-NaF PET/CT Findings of a Multiple Myeloma Patient With Thyroid Cartilage Involvement.

Thyroid cartilage is a very rare extramedullary involvement location in multiple myeloma. We present both F-NaF and F-FDG PET/CT findings of a multiple myeloma patient with thyroid cartilage involvement. In this patient, increased FDG and more intensely increased NaF uptake were seen on thyroid cartilage. In addition, some bone lesions had more intense NaF than FDG uptake, and some were only NaF avid. Although F-FDG PET/CT has an important role in plasma cell neoplasms, we considered that F-NaF PET/CT is also very useful to detect small lytic lesions that might be overlooked on F-FDG PET/CT.

Radioiodine uptake in an ovarian mature teratoma detected with SPECT/CT.

A 28-year-old woman underwent a near-total thyroidectomy for papillary carcinoma. Before radioiodine therapy, the serum thyroid-stimulating hormone level was 50 μIU/mL, the thyroglobulin level was 1 μg/L, and the antithyroglobulin was negative. She received 100 mCi of I for ablation of residual thyroid tissue. After therapy, I whole-body scan demonstrated focal uptake in the right pelvic area, which localized to the right ovary on SPECT/CT fusion images. The ovarian cyst was resected, and histopathological examination revealed a mature teratoma without thyroid tissue component. At 6-month follow-up, the whole-body radioiodine scan was normal, and serum thyroglobulin was undetectable.

Comparison of gated myocardial perfusion SPECT, echocardiography and equilibrium radionuclide ventriculography in the evaluation of left ventricle contractility.

OBJECTIVES In this study, we investigated the reliability of gated myocardial perfusion single-photon emission computerized tomography (GSPECT) for the evaluation of left ventricle (LV) function. We compared left ventricle ejection fraction (LVEF) calculated with GSPECT with the values derived from planar equilibrium-gated radionuclide ventriculography (ERVG) and echocardiography (ECHO). STUDY DESIGN Forty-eight patients with suspected coronary artery disease (CAD), who were referred for evaluation of myocardial perfusion and LV function and underwent two-day 99mTc-MIBI protocol GSPECT and ERVG, were examined retrospectively. LVEF was calculated with GSPECT Myometrix software, and wall motion and thickness were calculated with QGS analysis program. In the ERVG study, LVEF values were calculated using left anterior oblique images. In the GSPECT and ERVG study, wall motion was evaluated visually and scored. LVEF values and wall motion data measured with ECHO were noted. RESULTS For all cases, there was a significant correlation between LVEF values calculated by GSPECT and ERVG. Numerical LVEF values of 30 patients measured with ECHO showed no significant difference from the values measured with GSPECT. When 240 segments obtained from 48 patients were examined, the correlation between GSPECT and ERVG was 77.5% and between GSPECT and ECHO was 75.4% by visual wall motion analysis. Quantitatively calculated wall motion and thickness scores of segments visually defined as normokinetic were significantly higher than segments visually defined as having contraction defect. CONCLUSION GSPECT can be used safely in clinical practice for the evaluation of LV function. Quantitatively calculated wall motion and thickness scores are promising methods to verify the visual evaluation.

Scintigraphic Methods to Evaluate Alterations of Gastric and Esophageal Functions in Female Obesity

Objective: Altered gastrointestinal function has frequently been observed in obese patients. The aim of this study was to investigate the frequency of gastro-esophageal reflux (GER) and to determine the alterations of gastric emptying and esophageal transit by scintigraphic methods in obese patients. Methods: Scintigraphic studies of 50 obese female non-diabetic patients who had not received any treatment for weight control were retrospectively reviewed. Mean Body Mass Index (BMI) was 34.96±3.04 kg/m2 (range:32-39 kg/m2). All subjects were submitted to scintigraphic evaluation of esophageal transit, gastro-esophageal reflux, gastric emptying and presence of Helicobacter pylori infection. The data of obese patients were compared with those of sex-age matched 30 non-obese cases who were selected from our clinical archive. Results: In obese group, seventeen (34%) patients were found to be GER positive scintigraphically; mean gastric emptying time (t½) was 59.18±30.8 min and the mean esophageal transit time was 8.9±7.2 s. Frequency of positive GER scintigraphy and the mean value of esophageal transit time were significantly higher in obese patients than non-obese control subjects. Gastric emptying time and esophageal transit time values were significantly longer in GER positive obese patients than GER negative ones. There was no statistically significant difference in the frequency of positive C14 urea breath test between obese and non-obese subjects and there were also no statistically significant correlations between BMI, GER, esophageal transit time and gastric emptying time. Conclusion: In our study, 42 of the 50 obese patients had esophago-gastric motility alterations. The significance of these alterations in obesity is not fully understood, but it is believed that these changes could be because of potential contributing factors in the development or maintenance of obesity or changes in eating habits. Conflict of interest:None declared.