Gulseren Aras

Treatment for microcarcinoma of the thyroid--clinical experience.

Aims and Background: Papillary microcarcinoma of the thyroid is a specific subgroup of papillary thyroid carcinoma (PTC) and account for up to 30% of all PTC. According to the World Health Organization, papillary microcarcinoma of the thyroid (PMC) is defined as a papillary thyroid carcinoma measuring ≤10 mm in the greatest dimension. The relative rate of PMC is increasing in patients with differentiated thyroid carcinoma (DTC) mainly due to more frequent use and improvement of ultrasonography and fine-needle aspiration biopsy, and also more accurate histopathological examination of surgical specimens. The high incidence of PMC found in autopsy studies (up to 35%) suggests that most of them have a benign behavior. The locoregional recurrence has been reported in up to 20% of PMC patients and several cases of distant metastases have also been described. The ‘ideal’ therapeutic approach in PMC patients remains a subject of debate among endocrinologists and surgeons. Treatment of PMC in different departments varies from partial thyroidectomy to total thyroidectomy and radioiodine treatment. The main question in this group of patients is “How should PMC patients be treated?” The aim of this study was to investigate retrospectively the frequency and clinical behavior of PMC of the thyroid gland in our department and also to identify the optimal treatment of this group of patients. Materials and Methods: For this retrospective study, we evaluated 120 patients with PMC in our department (between 1997 and 2005). The mean age of patients at diagnosis was 43 ± 13 years (range 17–67 years). The female to male ratio was 87.5% (105 females, 15 males). The mean follow-up period of patients in this study was 45 months (16–84 months). Surgical treatment of patients with PMC in our department consisted of a bilateral total thyroidectomy in 25 patients (21%), and a bilateral near total thyroidectomy in 95 patients (79%). In the evaluation of our patients, multifocal PMC had a relative frequency of 15% (18/120 patients). The patients were informed about the different therapeutic strategies and the possible necessity for more frequent radioiodine treatment to eliminate thyroid remnants. All of the patients in our retrospective study had radioiodine (RAI) ablation therapy for residual thyroid tissue. Results: All patients received an RAI treatment dose which ranged from 75–150 mCi (2.7–5.5 GBq). Our criteria for ablation are as follows: negative I-131 WBS and very low serum Tg levels (<1 ng/mL). In 112/120 patients (93.3%), the thyroid remnant was ablated with a single dose of I-131 75–150 mCi (2.7–5.5 GBq). A second radioiodine treatment was necessary in 8 patients (7%), because of locoregional recurrence (required mean cumulative doses of 8.2–11 GBq I-131). Locoregional reccurence occurred in 2 patients with unifocal tumor, without capsular invasion or lymph node metastases and in 6 patients with multifocal tumor and/or in patients with capsular invasion or lymph node metastases. After a second radioiodine treatment, all of these 8 patients were ablated. All 120 patients remained free from disease (negative I-131 whole body scan, unmeasurable thyroglobulin levels) after a median follow-up period of 45 months and there was no recorded disease-related mortality. Conclusion: The treatment of patients with PMC should be no different from the treatment of patients with PTC, and thyroidectomy followed by radioiodine therapy may be a possible option for treatment of papillary microcarcinoma.

Brain SPECT findings in long-term inhalant abuse.

This study evaluates brain perfusion in long-term inhalant abusers of toluene, acetone, benzene and derivatives. Ten patients in the age range 16-18 years (mean, 17.3±0.67 years), who had been inhalant dependent for a mean period of 48.3±6.2 months, but who had stopped using inhalants for 1-11 months (mean, 5.4±2.1 months), and ten controls (mean age, 17.3±0.67 years) were included in the study. Psychiatric tests, biochemical tests and Tc-99m-hexamethylpropyleneamine oxime (Tc-99m-HMPAO) brain single photon emission computed tomography (SPECT) were performed on all patients. Brain SPECT images were evaluated qualitatively and quantitatively. The mean IQ level was found to be 84 (by psychological tests). Brain SPECT showed non-homogeneous Tc-99m-HMPAO uptake and hypoperfusion areas in all patients (five left temporal, one right temporal, two left temporal plus bilateral parietooccipital, one biparietal and one left temporoparietal). Seven patients had hyperperfused foci (unifocal in five patients and multifocal in two patients). Six hyperperfused foci were in a parietal and one in a temporoparietal location. This study suggests that inhalant dependents exhibit serious abnormalities in brain SPECT images, including hypo-hyperperfusion foci and non-homogeneous uptake of the radiopharmaceutical. A further study with a larger number of patients and long-term follow-up may help to reach a more specific conclusion.

The additive clinical value of 18F-FDG PET/CT in defining the recurrence of disease in patients with differentiated thyroid cancer who have isolated increased antithyroglobulin antibody levels.

Aim The aim of this study was to investigate the additive clinical value of 18F-FDG PET/CT in defining the recurrence of disease in patients with differentiated thyroid cancer (DTC) who have isolated increased antithyroglobulin antibody (TgAb) levels with undetectable thyroglobulin (Tg) levels and negative 131I whole-body scintigraphy (wbs). Materials and Methods Clinical follow-up data of 231 patients with DTC who underwent 18F-FDG PET/CT between June 2006 and March 2011 were evaluated retrospectively. There were a total of 48 patients who underwent 18F-FDG PET/CT for isolated increased serum TgAb levels. When 17 patients who have lymphocytic thyroiditis were excluded, the remaining 31 patients [27 women and 4 men; mean (SD) age, 50.29 (15.2) y] were included in this study. The inclusion criteria were undetectable serum Tg and increased TgAb levels under the condition of thyroid-stimulating hormone greater than 30 IU/mL with negative 131I wbs and absence of pathologic findings in neck ultrasound and thoracic CT if performed. Findings from the 18F-FDG PET/CT were compared with the clinical follow-up data and the results of histopathologic examinations. Results Results of 18F-FDG PET/CT were negative in 15 and positive in 16 patients. Sixteen FDG-positive sites (15 lymph nodes and 1 bone) were seen in 16 patients who had positive findings in 18F-FDG PET/CT. In the comparison with 18F-FDG PET/CT findings and clinical follow-up data and histopathologic examination results, 4, 12, 2, and 13 patients were false-positive, true-positive, false-negative and true-negative retrospectively. In the receiver operating characteristic analysis, a 5.4 cutoff SUVmax value was calculated with 82% sensitivity and 81% specificity in distinguishing malignant and benign lesions. As a result, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18F-FDG PET/CT in the detection of recurrent disease were calculated as 75%, 76%, 75%, 86%, and 80%, respectively. Conclusions Isolated increased TgAb levels might be a predictor of the recurrent DTC and 18F-FDG PET/CT might be an additive imaging method in detecting the recurrent disease in patients with DTC who have increased TgAb levels with undetectable Tg levels and negative 131I wbs.

Palliative analgesic effect of Re-186 HEDP in various cancer patients with bone metastases

The clinical picture of bone metastases is manifested by pain and loss of mechanical stability. Standard treatment options for bone metastases include external beam radiotherapy and the use of analgesics. Due to a large number of lesions in many patients, the use of radionuclide therapy with beta emitters may be preferable. Re-186 hydroxyethylidene diphosphonate (Re-186 HEDP) is one of the radiopharmaceuticals suitable for palliative treatment of metastatic bone pain. The aim of this study was to investigate palliative and side effects of Re-186 HEDP in patients with different types of cancers.Material & Method: Thirty one (17 male, 14 female) patients with various cancers (10 prostate, 10 breast, 4 rectum, 5 lung, 2 nasopharynx) and bone metastases were included in the study. Therapy was started with a fixed dose of 1295 MBq of Re-186 HEDP. If necessary, the same dose was repeated at least 3 times after an interval of 10–12 weeks; A total of 40 standard doses were given; 6 patients received repeated doses (3 doses in 3 patients, 2 doses in 3 patients). The patients with bone marrow suppression were excluded from the study. The pain relief was assessed the Eastern Cooperative Oncologic Group (ECOG) and the Karnofsky status index. All patients were evaluated with standard evaluation forms filled in daily for a maximum of 10 weeks.Results: The mean response rate was 87.5% in patients with breast and prostate cancer, 75% in patients with rectum cancer and 20% in patients with lung cancer. The overall response rate was 67.5%. The palliation period varied between 6 and 10 weeks, with a mean of 8.1±1.3 weeks. The maximal palliation effect was observed between the 3rd and 7th weeks. No serious side effects were seen except mild hematologic toxicity.Discussion & Conclusion: It is concluded that Re-186 HEDP is a highly effective agent in the palliation of metastatic bone pain in patients with prostate, breast and rectum cancer, but not effective in lung cancer. On the other hand, Re-186 seems to be a good alternative to Sr-89 because of its preferable physical characteristics (such as short half life and gamma energy emission), low side effect profile, early response and repeatability.

Correlation of 18F-FDG PET/CT findings with histopathological results in differentiated thyroid cancer patients who have increased thyroglobulin or antithyroglobulin antibody levels and negative 131I whole-body scan results.

Aim This study aimed to investigate the correlation of 18F-FDG PET/CT findings with histopathological results in defining the recurrence of the disease in patients with differentiated thyroid cancer (DTC) who have increased thyroglobuline (Tg) or anti-Tg antibody (TgAb) levels and negative 131I whole-body scan (WBS) result. Patients and Methods A total of 59 patients with DTC (44 women, 15 men; mean [SD] age, 48.2 [22.6] years) were included in the study. All of the patients had previous papillary thyroid cancer, and all of them had undergone radioiodine ablation after a total or near-total thyroidectomy. After radioiodine ablation, patients were followed up for approximately 2.5 years. In the follow-up, the patients with negative 131I-WBS results and increased Tg or TgAb levels under thyroid-stimulating hormone–stimulated conditions underwent an 18F-FDG PET/CT scan to determine any recurrence of disease. There were negative or uncertain findings in the neck ultrasonography and/or thorax CT in most of the patients. The 18F-FDG PET/CT findings were compared with the histopathological results in all patients. Results Although 49 patients had increased Tg levels, the remaining 10 patients had increased TgAb levels. In patients with high Tg levels, 18F-FDG PET/CT scan results were negative in 10 and positive in 39 patients. In this patient group, 18F-FDG PET/CT findings were true positive, true negative, false positive, and false negative in 32, 3, 7, and 7 patients, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT in this group were calculated as 82%, 30%, 80%, 30%, and 71%, separately. In the receiver operating characteristic analysis, a 4.5 cutoff SUVmax was calculated with 75% sensitivity and 70% specificity for predicting disease recurrence. Cutoff Tg level was calculated as 20.7 ng/mL with 75% sensitivity and 55% specificity. In 10 patients with high TgAb levels, 18F-FDG PET/CT was true positive, true negative and false positive in 6, 2, and 2 patients, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT in this patient group were calculated as 100%, 50%, 75%, 100%, and 80%, respectively. Conclusions 18F-FDG PET/CT may be a useful imaging modality in defining recurrence of the disease in patients with DTC who have increased Tg or TgAb levels, negative 131I-WBS results, and negative or suspicious neck ultrasonography and/or thorax CT results. Although 18F-FDG PET/CT seems to be a more sensitive method in patients with increased TgAb levels, the number of patients is not enough to make a substantiated comment.

Radioiodine whole-body scans, thyroglobulin levels, 99mTc-MIBI scans and computed tomography : results in patients with lung metastases from differentiated thyroid cancer

ObjectivesThe correlation between a 131I whole-body scan (WBS), a 99mTc sestamibi (99mTc-MIBI) WBS, a computed tomography (CT) scan and the value of routine follow-up for 131I WBS and thyroglobulin (Tg) levels in patients with lung metastases from differentiated thyroid cancer was assessed. MethodPulmonary metastases were detected in 32 patients out of 583 with differentiated thyroid cancer (DTC) who were admitted to our clinic between 1985 and 2004 (age range, 22–79 years; mean, 58±19 years; 15 women and 17 men). Pulmonary metastases were diagnosed by considering the 131I WBS, increased Tg levels and/or other positive radiological findings. Papillary carcinoma was diagnosed in 15/32 patients and follicular carcinoma in 13/32. A mixed type found in 4/32 patients was classified histopathologically. A total of 3.7–53.65 GBq (100–1450 mCi) 131I was given to each patient. The duration of follow-up ranged from 36 to 240 months. A 131I WBS, the determination of Tg levels and/or a CT scan were carried out in the assessment of a diagnosis and follow-up of patients with lung metastases. A 99mTc-MIBI WBS was performed on 19 patients who were chosen at random from the 583. ResultsNineteen of 32 patients had lung metastases before they received the first 131I treatment. Six of the 32 had distant-organ metastases other than in the lungs. Four of these six patients had only lung and bone metastases. Pulmonary metastases were observed on the 131I WBS patients 31/32 (96.8%) whereas no pulmonary metastases, were detected on the CT scans in 3/32 patients. The last diagnostic whole-body scan (DWBS) was normal in 13/32 patients. At the first examination, the Tg levels in 27/32 (84.4%) patients were below 30 ng · ml−1. At the final examination, 20/32 (62.5%) patients had Tg levels higher than 30 ng · ml−1, while Tg levels were lower than 30 ng · ml−1 in 12/32 patients. Tg levels decreased in 21/32 and increased in 3/32 patients. The 131I WBS continued to be abnormal in 2/3 patients with increased Tg levels but became normal in one patient whose CT scan still showed macro-nodular lesions. Tg levels did not change significantly in 8/32 patients. The 131I WBS became normal in 5/8 patients, while the CT scans for 4/5 showed micro-nodules. Metastases were detected in 12/19 patients who underwent 99mTc-MIBI whole-body scanning: 18/19 showed metastases on the 131I WBSs and 17/19 on the CT scans. Of the seven patients without a sign of metastasis on the 99mTc-MIBI WBS, one was negative in terms of metastasis on the 131I WBS and one on the CT scan. Fibrosis was observed on the CT scans of 2/32 patients. One patient developed dedifferentiation, as determined by the negative 131I WBS and positive CT scan. Conclusion131I whole-body scanning and the determination of Tg levels are the most important procedures for the evaluation of lung metastases in differentiated thyroid cancer. Computed tomography is a useful addition to 131I whole-body scanning. MIBI imaging alone may not be enough to detect lung metastases from differentiated thyroid cancer.

The role of 18F–NaF PET/CT in metastatic bone disease

Aim To investigate the role of 18F–NaF PET/CT and compare it with 99m Tc-MDP whole body bone scintigraphy and 18F-FDG PET/CT in detecting the extent of metastatic bone disease and to present our first experience with 18F–NaF PET/CT in our country. Materials and methods A total of 37 histopathologically proven cancer patients (22 male, 15 female) with bone metastasis detected on Tc-99m MDP whole body bone scan were prospectively enrolled Cebeci, following ethics committee approval. 18F–NaF PET/CT was performed to the participants in Ankara University Medical Faculty Nuclear Medicine Department for evaluation of symptomatic skeletal sites which were negative on Tc-99m MDP whole body bone scan. A lesion based comparison was made between 18F–NaF PET/CT and Tc-99m MDP whole body bone scan for each patient and between 18F–NaF PET/CT and 18F-FDG PET/CT in 12/37 patients. Results The number of lesions demonstrated by 99m Tc-MDP bone scan and 18F–NaF PET/CT was equal in 4/37 (%11) of the cases. 18F–NaF PET/CT showed a greater number of pathological foci in 89% of participants. 18F–NaF PET/CT was able to show both lytic and blastic lesions and small lesions were better visualized due to the advantage of sectional imaging with much better resolution and higher target/background ratio. 18F–NaF PET/CT demonstrated a greater number of metastases in 10/12 (83%) of the patients when compared to 18F-FDG PET/CT. In the other two patients, bone metastasis could be demonstrated only by 18F–NaF PET/CT. The uptake of 18F-FDG was variable in blastic lesions and cranial bone involvement was missed by 18F-FDG PET/CT in some cases due to physiological brain metabolism. Conclusion Although further prospective clinical studies in specific cancer populations are indicated to set the place of 18F–NaF PET/CT in diagnostic scheme, the results of this pilot study from our country support the superiority of 18F–NaF PET/CT in investigation of bone metastasis over 99mTc-MDP bone scan and 18F-FDG PET/CT in various malignancies. 18F–NaF PET/CT is coming forward as a single step bone seeking study, considering all the advantages, but especially potential of detecting occult metastases and reliably directing patient management.

Evaluation of cardiac functions in patients with thalassemia major

It is known that a blood transfusion is necessary for survival in patients with thalassemia, but it may cause myocardial dysfunction due to myocardial siderosis as in other organs. The aim of this study was to evaluate myocardial perfusion by means of stress thallium scanning (MPS) and left ventricular functions by rest radionuclide ventriculography (RNV).Twenty-one patients at ages 9–16 (mean 12.1 ± 3.2) who have been diagnosed with thalassemia for 4–15 years (mean 12.7 ± 4.8) were included in the study. They had blood transfusions 78–318 times (mean 162.1 ± 71). MPS and RNV was performed within two days after the any transfusion. MPS showed ischemia in 3 patients and normal perfusion in 18 patients. RNV revealed normal systolic parameters (wall motion, EF, PER, TPE) but diminished diastolic parameters (TPF, PFR) compared with normal values (p < 0.05).We conclude that ischemia or fixed defects may be seen in stress MPS as a result of cardiac involvement in patients with thalassemia. But, RNV is an important and preferable test for the early detection of subclinic cardiomyopathy. RNV may therefore show diastolic abnormalities before the systolic abnormalities show up.

The additive clinical value of combined thyroglobulin and antithyroglobulin antibody measurements to define persistent and recurrent disease in patients with differentiated thyroid cancer.

AimTo evaluate retrospectively the additive clinical value of combined thyroglobulin (Tg) and antithyroglobulin antibody (TgAb) measurements to define recurrent and persistent disease in patients with differentiated thyroid cancer. Materials/methods181 patients with differentiated thyroid cancer were included in the study. The nonstable disease group (recurrent and persistent disease) had 61 patients with 24–36 months follow-up period. The stable disease group (without recurrence or persistence) had 120 patients with 21–28 months follow-up period. We compared Tg and combined Tg–TgAb levels on the sixth month after the ablation between two groups. ResultsOptimal threshold values for Tg, TgAb measurements were calculated statistically as 4.45 ng/ml and 27.8 IU/ml. Optimal sensitivity and specificity for 4.45 ng/ml Tg levels were 52.5 and 91.7%. We also evaluated different Tg threshold values. We found sensitivity was 54.2% and specificity 86.7% for 2 ng/ml and sensitivity was 40.7% and specificity 96.7% for 10 ng/ml Tg levels. By the odds ratio (OR) rule, the obtained sensitivity and specificity were 68.3 and 90% (if Tg>10 ng/ml or TgAb>27.8 IU/ml), 78.3 and 90% (if Tg>4.45 ng/ml or TgAb>27.8 IU/ml), and 80% and 85% (if Tg>2 ng/ml or TgAb>27.8 IU/ml). Sensitivity increased with statistical significance from 52.5 to 78.3% (P<0.001) and decreased with statistical insignificance from 91.7 to 90% (P>0.05) for the optimal thresholds. ConclusionCombined Tg–TgAb values were found more useful than only Tg for recurrent and persistent diseases. Combined Tg and TgAb measurements seemed to be a useful marker.

Clinical importance of technetium-99m-methoxyisobutylisonitrile (MIBI) scintigraphy in differentiated thyroid carcinoma patients with elevated thyroglobulin levels and negative I-131 scanning results

Aims and BackgroundThe aim of this study was to evaluate the potential contribution of Tc-99m-MIBI scintigraphy to the follow-up of patients with differentiated thyroid carcinoma, who had elevated Tg levels and negative I-131 whole-body scan results.Materials and MethodsIn this retrospective study, we evaluated 28 patients with differentiated thyroid carcinoma, who had total or near total thyroidectomy followed by an ablative dose of I-131 at various time intervals (15 women, 13 men; mean age 43 ± 17 years). All patients were treated with T4 suppression. After a mean follow-up period of 6.1 years (range 3–15) all patients were determined to have a high serum Tg concentrations (>2 ng/ml) and previous negative I-131 WBS results. All patients were examined for metastatic sites using Tc-99m-MIBI scan. Scans were visually evaluated for detecting lymph node metastases and/or local recurrence, lung metastases and skeletal metastases.ResultsTc-99m-MIBI scan demonstrated lesions in 23 patients (83.3%). In five patients with negative Tc-99m-MIBI scan findings (FN results): * Chest CT showed small-sized mediastinal LN metastases in 2 patients and lung metastases in another 2 patients (<1 cm). * Neck CT showed small-sized cervical LN involvement in 1 patient. The sensitivity of detection for neck was 94.4%, for lung 63.6%, and for bone lesions 100%. For all scan sites taken together, the sensitivity of disease detection was 83.3%, the specificity was 50%, positive predictive value (PPV) was 96.2%, and finally negative predictive value (NPV) was 16.7%.ConclusionWe concluded that Tc-99m-MIBI scan should be considered as a supplementary scintigraphic method for the follow-up of patients with high serum Tg levels and negative I-131 WBS results, and it can help clinicians in making the decision to treat these patients.