Çetin Önsel

Treatment of iodine-negative thyroglobulin-positive thyroid cancer: differences in outcome in patients with macrometastases and patients with micrometastases.

PurposeDuring the follow-up of patients with well-differentiated thyroid carcinoma, some patients have elevated serum thyroglobulin (Tg) levels without any evidence of radioiodine accumulation on diagnostic whole-body scan (d-WBS). The treatment strategy in these patients is considered a clinical dilemma, with some groups recommending blind use of high-dose radioiodine therapy. The aim of this study was to evaluate whether or not high doses of radioiodine have beneficial effects in these patients.MethodsTwenty-seven patients were included in the study. All patients had negative d-WBS and elevated levels of Tg. All received high doses of radioiodine. The mean follow-up period was 6.3±5.8 years. There were 11 patients with macrometastases and 16 with micrometastases.ResultsPost-treatment WBS revealed radioiodine accumulation in 19 of 24 (79%) patients. Serum Tg levels were decreased in 8 of 16 (50%) patients. Among patients with micrometastases, five out of seven (71%) demonstrated a decrease in serum Tg levels. Among patients with macrometastases, three out of nine (33%) demonstrated a decrease in Tg values and three (33%) have died due to metastatic thyroid cancer.ConclusionRadioiodine treatment may have a beneficial therapeutic effect in patients who have elevated levels of serum Tg and negative d-WBS. This is especially true in those patients with micrometastases; in patients with macrometastases, a beneficial effect of this approach may be observed less frequently.

Impact of initial surgical treatment on survival of patients with differentiated thyroid cancer : Experience of an endocrine surgery center in an iodine-deficient region

This retrospective clinical study was designed to analyze the impact of the initial surgical procedure on the survival of 1000 patients with differentiated thyroid cancer of follicular cell origin who had a thyroid operation and were followed for the 30 years between 1968 and 1998 (median 14 years) in an iodine-deficient region where goiter is endemic. There were 753 women and 247 men with a mean age of 42.8 ± 6.7 years (range 17–86 years). Patients were divided into three groups. All patients had undergone thyroxine treatment and thyroid-stimulating hormone (TSH) suppression, and most had had iodine-131 treatment postoperatively. Group A consisted of 336 patients with differentiated thyroid cancer (DTC) who were treated with bilateral subtotal thyroidectomy in our institution or elsewhere. Group B consisted of 158 patients with DTC who were treated initially with unilateral total lobectomy and contralateral subtotal lobectomy in our institution or elsewhere and underwent reoperation in our department. Group C consisted of 506 patients with DTC who were treated initially with total or near-total thyroidectomy in our department. Kaplan-Meyer survival analysis was used. Recurrence was seen in 23% and death in 8% of the patients. The 20-year survival rates were 76%, 85%, and 92% for groups A, B, and C, respectively. The survival difference among the patients of group A and groups B and C was found to be statistically different (p < 0.001). Long-term survival of patients with differentiated thyroid cancer living in endemic areas for goiter can be influenced by the initial surgical treatment. Patients treated initially with total or near-total thyroidectomy appear to have a better prognosis.

Correlation of technetium-99m MIBI and thallium-201 retention in solitary cold thyroid nodules with postoperative histopathology

Abstract.A comparative prospective study of technetium-99m methoxyisobutylisonitrile (MIBI) and thallium-201 with early (15 min) and delayed (90 min for MIBI, 3 h for 201Tl) imaging in the differentiation of thyroid lesions is presented. Forty patients with cold thyroid nodules visualised on 99mTc-pertechnetate scan and with dyskaryotic or atypical epithelial cells verified by fine-needle aspiration biopsy underwent MIBI and 201Tl scintigraphy at 3-day intervals. Subsequent thyroidectomies were carried out in all patients. Semiquantitative analysis was performed using a lesion to non-lesion ratio on early (ER) and delayed images (DR). Additionally, a retention index (RI) was calculated using the formula RI=(DR– ER) × 100/ER. The reproducibility of the method for the early and delayed measurements was tested by analysing intra- and inter-observer variability and repeatability coefficients. Histopathologically, the nodules were found to be well-differentiated thyroid cancer in 21 patients and benign in 19 patients. There was no significant difference in the ER between malignant and benign lesions for either 201Tl or MIBI (P>0.05). However, for both agents significant differences were found between malignant and benign lesions with regard to DR (P<0.01 for 201Tl and P<0.001 for MIBI) and RI (P<0.001 for both agents). Statistical comparison of the two agents showed no significant differences (P>0.05) except with regard to DR and RI in malignant nodules (P<0.05). A receiver operating characteristic analysis was performed to determine threshold levels for the differentiation of malignant from benign nodules. Following this analysis, ER, DR and RI levels of 1.03, 1.54 and 2 for MIBI and ≤1.42, 1.24 and 5 for 201Tl were selected. Using these threshold levels, the sensitivity, specificity and accuracy of the study were 90.5%, 36.8% and 65% for ER MIBI, 61.9%, 94.7% and 77.5% for DR MIBI, 95.2%, 89.4% and 92.5% for RI MIBI, 85.7%, 47.3% and 67.5% for ER 201Tl, 80.9%, 73.6% and 77.5% for DR 201Tl, and 90.5%, 94.7% and 92.5% for RI 201Tl. In conclusion, the DR for MIBI and 201Tl is superior to the ER in detecting malignant nodules, and the RI for both MIBI and 201Tl is more valuable than the DR in differentiating malignant from benign thyroid nodules.

Effects of allopurinol, ibuprofen and cyclosporin A on local microcirculatory disturbances due to burn injuries

This experiment was designed to study the reactions in the surrounding area of burn injury that may lead to further necrosis in 24 h. To prevent extension of burn size into the tissue adjacent to burn injury, it was attempted to reduce progressive microvascular damage by different drugs (ibuprofen, allopurinol or cyclosporin A (CyA)) in a rat model. The burn model consisted of a row of four 10 x 20 mm burn areas separated by three unburned 5 x 20 mm skin bridges (interspaces). To evaluate microcirculation and perfusion of panniculus carnosus muscle which is beneath the burned area of skin, the radioactive agent, technetium-99m methoxyisobutylisonitrile (99Tc01-MIBI) was used 24 h after the burn. Capillary permeability of injured tissue was assessed by the wet and dry weight technique. In all study groups, interspaces showed higher uptakes of 99Tc01-MIBI between 40 and 95 per cent, in comparison with burn sites in the first 24 h following burn. Among the treated rats better results were obtained by allopurinol and CyA treatment that commenced before burn than ibuprofen. Wet and dry ratios were found to be significantly lower in interspaces in rats pretreated with allopurinol and CyA. Results of this experiment showed that neutrophils and free radical-mediated injury may be involved in the pathogenesis of local response to thermal injury, and allopurinol and CyA have some effects to prevent progressive ischemia, capillary compromise and oedema.

The effect of P-glycoprotein function inhibition With cyclosporine A on the biodistribution of Tc-99m sestamibi

PURPOSE The failure to cure persons with cancer is caused primarily by the development of drug resistance by overexpression of p-glycoprotein. Diverse groups of drugs have been identified, including cyclosporine A, which can reverse drug resistance by inhibiting P-glycoprotein transport. Tc-99m sestamibi is a substrate for P-glycoprotein. P-glycoprotein is normally expressed in biliary canalicular surfaces of hepatocytes and is responsible for the excretion of cationic metabolites from the liver. The aim of the current study was to evaluate the effect of cyclosporine A on the biological distribution of Tc-99m sestamibi in vivo. METHODS Five patients with alopecia and two renal transplant patients who were treated with cyclosporine A were selected for the study. All patients were examined before and at least 2 weeks after administration of cyclosporine A. Tc-99m sestamibi scintigraphy was performed by obtaining planar abdominal images at 5, 30, 60, 120, and 180 minutes after injection, and the liver-heart ratios were calculated. RESULTS Plasma cyclosporine A, bilirubin levels, liver enzymes, and creatinine clearance values were obtained from all patients. In three, the plasma cyclosporine A level was increased to more than 400 pg/dl. The liver-heart ratio was increased significantly after cyclosporine A administration (P < 0.01). After cyclosporine A administration Tc-99m sestamibi excretion was delayed and the uptake in the liver was increased. The difference was 17% at 5 minutes and 38% at 180 minutes. Liver retention was greatest in patients with cyclosporine A toxicity. CONCLUSIONS With a limited number of patients, this study suggests that Tc-99m sestamibi excretion from the liver is mediated by P-glycoprotein, and inhibition of P-glycoprotein transport not only delays liver excretion but also increases the liver uptake of Tc-99m sestamibi. Because this observation deserves further investigation, the inhibition of P-glycoprotein function with nontoxic multidrug-resistance reversing agents may be used as an intervention to increase the tumor uptake of Tc-99m sestamibi and to increase the sensitivity of Tc-99m sestamibi tumor imaging.

The Diagnostic Role of FDG PET/CT in Patients with Fever of Unknown Origin.

Objective: Fever of unknown origin (FUO) is a challenge for the physician and needs use of clinical, laboratory, and imaging studies and also invasive and/or non-invasive interventions to detect the etiology. The aim of present study was to assess the role of FDG PET/CT in determining the etiology in patients with FUO. Material and Methods: Twenty-four patients (median age 52, range 5-77 years, 6 female, 18 male) who were diagnosed with FUO were retrospectively analyzed in this study. Before the FDG PET/CT studies, none of them had a definitive reason for their diseases investigated by conventional radiological or scintigraphic methods, clinical and laboratory observations. Results: The positive result was achieved in 19 (79.2%) of 24 patients as findings of the FDG PET/CT. However, FDG PET/CT was useful for definitive diagnosis in 12 (63.2%) of 19 positive patients. Malignant diseases were determined to be the underlying cause of FUO in 5 (41.6%) of 12 patients. Noninfectious inflammatory causes were detected in 2 (16.7%) patients, infections were exhibited in 3 (25%) patients, and miscellaneous diseases demonstrated in 2 (16.7%) patients. In 7 patients the detected pathological uptakes on FDG PET/CT were not helpful for the definitive diagnosis. In remaining 5 patients who showed no pathological uptake in the FDG PET/CT, diagnosis could not be established by other methods, as well. The sensitivity, specificity, and positive and negative predictive values for the determination of FUO etiology were 92.3%, 45.4%, 63.1%, and 100% for FDG PET/CT. Conclusion: Our results demonstrate that FDG PET/CT seems to have considerable contribution to reveal the reason of undiagnosed patients with FUO investigated by conventional diagnostic methods, clinical and laboratory observations. Conflict of interest:None declared.

The role of 99Tcm-tetrofosmin in the evaluation of thyroid nodules

Various radionuclides, including 67Ga, 201Tl and 99Tcm-sestamibi, have been used to differentiate benign from malignant thyroid nodules. 99Tcm-tetrofosmin, a lipophilic cationic radiotracer, and 99Tcm-sestamibi have also been reported to accumulate in thyroid tumours. In this study, we evaluated the role of 99Tcm-tetrofosmin in the differentiation of malignant from benign thyroid nodules. Seventy-nine patients with solitary non-functioning thyroid nodules were included in the study. Fine-needle aspiration biopsy was performed in all patients. Sixty patients were subsequently operated on and 19 patients refused surgery. After the injection of 370 MBq 99Tcm-tetrofosmin, static images at 5, 30, 60, 120 and 180 min were acquired. Both visual and semi-quantitative analysis was performed. On visual interpretation, the nodules with late retention were classified as positive for malignancy and nodules without late retention were classified as negative for malignancy. In the semi-quantitative analysis, regions of interests were drawn over the nodule and contralateral normal thyroid tissue. The average number of counts was recorded and tumour-to-normal thyroid tissue ratios calculated. Post-operative histology revealed 19 malignant and 41 benign nodules. Of the benign nodules, adenomas behaved similarly to the malignant nodules with late retention of tracer, while adenomatous nodules revealed no late retention on delayed images and could be differentiated from malignant tumours. In the semi-quantitative analysis, there was a significant difference in tumour-to-normal tissue ratios for adenomatous nodules and malignant tumours as well as adenomas. We conclude that it is not possible to differentiate between malignant and benign thyroid nodules with 99Tcm-tetrofosmin. However, 99Tcm-tetrofosmin scintigraphy is helpful in selecting nodules that can be cured by surgical intervention.

Single-photon emission computed tomographic myocardial perfusion imaging in patients with mitral valve prolapse.

The possibility of exercise-induced myocardial ischemia due to mitral valve prolapse (MVP) in the absence of coronary artery disease was evaluated with single-photon emission computed tomographic analysis using thallium-201 and technetium-99m sestamibi in 72 patients with MVP. Exercise electrocardiography was positive in 5 patients (8%), but single-photon emission computed tomography was found to be normal in all patients, and exercise-induced chest pain, electrocardiographic changes, and arrhythmias were found not to be related to myocardial ischemia in patients with MVP.

Comparison of 99mTc-HYNIC-TOC and HYNIC-TATE octreotide scintigraphy with FDG PET and 99mTc-MIBI in local recurrent or distant metastatic thyroid cancers.

Aim There have been various studies for early diagnosis of local recurrent or distant metastatic thyroid cancers. The aim of this study is to evaluate the clinical utility of 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE, octreotide derivatives, to detect recurrences or distant metastases in 131I-negative thyroglobulin positive thyroid cancer patients and to compare the lesions with FDG PET and 99mTc-MIBI studies in the same patient group. Patients and Methods Twenty differentiated thyroid cancer patients, 7 male and 13 female, mean age 54.6 ± 15.3 (range 13–78 years), were included in this study. Eighteen patients had papillary thyroid cancer and 2 had follicular thyroid cancer. Fifteen patients received HYNIC-TOC and 5 patients received HYNIC-TATE as a radiopharmaceutical. All patients underwent whole-body scan 1 and 4 hours after injection of octreotide derivatives and SPECT imagings were performed from the suspicious sites. The lesions that were seen in 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE studies were compared with 99mTc-MIBI and FDG-PET studies. Results Among 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE scintigraphies, 15 patient studies were evaluated as true positive (75%) and 5 were false negative (25%). The total number of lesions in octreotide scintigraphy was 48 in 20 patients. Of 20 patients, 19 had FDG-PET study, 15 of them were evaluated as true positive (78.9%), and 4 them were evaluated as false negative (21.1%). Total number of lesions in FDG PET was 74. 99mTc-MIBI study was positive in 11 patients (55%) and negative in 9 patients (45%). Total number of lesions in 99mTc-MIBI was 25. Conclusion Technetium-labeled somatostatin receptor scintigraphy analogues HYNIC-TOC and HYNIC-TATE are useful imaging alternatives in somatostatin receptor expressing thyroid cancer patients. Radiolabeling is easy and they are readily available for routine use.

Temporal relationship between gastroesophageal reflux and rate of gastric emptying in children.

ObjectivesThere are conflicting reports for the relationship of reflux and the gastric emptying rate. In addition, the acquisition period is not well defined for the gastroesophageal reflux studies. The aim of our study was to evaluate the temporal distribution of the reflux episodes and to evaluate whether the gastric emptying rate changed with the gastroesophageal reflux time or amount. MethodsWe used radionuclide scintigraphy to evaluate 211 pediatric patients (0–10 years of age). Scintigraphic studies were performed by acquiring 15 s images for 1 h in a supine position after ingesting milk containing 0.5 mCi (18.5 MBq) Tc-99m colloid. Reflux episodes were calculated every 10 min for each patient who had reflux. The gastric emptying rate was measured by drawing an region of interest over the gastric activity. ResultsGastric reflux was observed in 104 patients (49.28%). The number of reflux episodes was higher in the first and second 10 min (33.7 and 29.1% respectively). The lowest reflux episode was observed in the last 10 min (between 50 and 60 min) (2.6%) suggesting that the reflux episode was decreasing by the gastric emptying. Within the first 30 min, reflux was observed in 98 of 104 patients (94.23%). The gastric emptying rate was calculated to be 73 min in patients with a higher incidence of reflux and 62 min in patients who had delayed and lower incidence of reflux episodes. In 104 patients, the average gastric emptying rate was 71.60 min. There were no significant differences in the gastric emptying rates between patients who had reflux episodes beginning in the first 30 min of the study and those who had reflux episodes in the last 30 min of the study (P>0.05). ConclusionThis study has suggested that the number of reflux episodes were not related with the gastric emptying rate. However, reflux could be observed in a higher frequency before gastric emptying, which also suggested that a 30-min period may be sufficient when reflux is shown early. In negative cases, a 60-min acquisition time is recommended for the diagnosis of gastroesophageal reflux.