Peter Mikosch

F-18 fluorodeoxyglucose positron-emission tomography in the diagnosis of tumor recurrence and metastases in the follow-up of patients with breast carcinoma: a comparison to conventional imaging.

Aim.To evaluate the role of F-18-fluorodeoxyglucose positron-emission tomography (F-18 FDG PET) in the follow-up of breast carcinoma in case of clinical suspicion of local recurrence or distant metastases and/or tumor marker increase in correlation to conventional imaging. Material and Methods.Retrospective analysis of the results of F-18 FDG PET (ECAT ART®, Siemens CTI MS) of 62 patients (age 58.5 ± 12.8) with surgically resected breast carcinoma (time interval after surgery, 86 ± 82 months, mean follow-up 24 ± 12.6 months). Patient- and lesion-based comparison with conventional imaging (CI) including mammography (MG), ultrasonography (US), computerized tomography (CT), magnetic resonance imaging (MRI), radiography (XR) and bone scintigraphy (BS). Furthermore, we evaluated the influence on tumor stage and therapeutic strategy. A visual qualitative evaluation of lesions was performed. Results.On a patient base, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for detecting local recurrence or distant metastases were calculated to be 97%, 82%, 87%, 96% and 90% compared with 84%, 60%, 73%, 75% and 74% with CI. On a lesion base, significantly more lymph node (84 vs. 23, P < 0.05) and fewer bone metastases (61 vs. 97, P < 0.05) could be detected by using F-18 FDG PET compared with CI. Sclerotic bone lesions were predominantly detected by BS. On the other hand, there were several patients with more FDG positive bone lesions and also mixed FDG positive/Tc-99m methylenediphosphonate (MDP) negative and FDG negative/Tc-99m MDP positive metastases. In case of normal tumor markers, sensitivity, specificity, PPV, NPV and accuracy for detecting local recurrence or distant metastases were calculated to be 100%, 85.0%, 78.6%, 100% and 90.3% for FDG PET and 80%, 50%, 50%, 80% and 61.5% for CI. An upstaging could be observed in 9.7% (6/62) and downstaging in 12.9% (8/62), leading to a change in therapeutic regimen in 13 patients (21%). Conclusions.F-18 FDG PET demonstrates apparent advantages in the diagnosis of metastases in patients with breast carcinoma, compared with conventional imaging on a patient base. On a lesion base, significantly more lymph node and less bone metastases can be detected by using F-18 FDG PET compared with conventional imaging, including bone scintigraphy. In patients with clinical suspicion but negative tumor marker profile, too, F-18 FDG PET seems to be a reliable imaging tool for detection of tumor recurrence or metastases. Considering the high predictive value of F-18 FDG PET, tumor stage and therapeutic strategy will be reconsidered in several patients.

Attenuation-corrected thallium-201 single-photon emission tomography using a gadolinium-153 moving line source: clinical value and the impact of attenuation correction on the extent and severity of perfusion abnormalities

Abstract. The aim of the study was to test the clinical value of attenuation-corrected (AC) thallium-201 single-photon emission tomography using a moving gadolinium-153 line source in a group of patients in whom coronary angiography was planned because of clinically suspected coronary artery disease (CAD). Furthermore, we wanted to test the impact of AC on assessment of the extent and severity of perfusion abnormalities. A total of 107 patients planned to undergo coronary angiography were included in the study. In each patient, AC and NC (non-corrected) 201Tl SPET was performed. AC and NC images were evaluated visually as well as by a 31-segment semiquantitative analysis and the findings were correlated with angiographic results. Patients were assigned to two groups: group A with angina and no previous cardiac infarction or intervention and group B with known CAD because of previous myocardial infarction or intervention. With visual analysis, NC revealed a sensitivity of 88.9% in group A and 74.3% in group B, compared to 94.4% in group A and 94.3% in group B with AC. Specificity for NC was calculated to be 68.7% for group A and 91.3% for group B. AC demonstrated significantly higher specificity of 83.9% and 100%, respectively. This effect was particularly demonstrated for males and bicycle workload. The extent and severity of perfusion abnormalities were significantly influenced by the use of AC, in that significantly fewer abnormal and less severely abnormal segments were demonstrated in the segmental analysis as compared to NC; this was especially true for the vascular territory of the left anterior descending artery nd the right coronary artery. It is concluded that AC with a moving line source is feasible in patients with all degrees of probability of CAD. AC has a significant impact on the assessment of the severity and extent of myocardial ischaemia, especially in the posterior and septal wall.

Iodine supplementation in Austria: methods and results.

Until 1963 Austria was an extremely iodine-deficient area with low iodine intake and high goiter prevalence. Therefore, for the first time in 1963, salt iodination with 10 mg of potassium iodide per kilogram of salt was introduced by federal law. Twenty years after this salt iodination, however, investigations in schoolchildren demonstrated iodine deficiency grade I to II according to the World Health Organization (WHO) (urinary iodine excretion, 42-75 microg/g Crea) and goiter prevalence of far more than 10%. In 1990, salt iodination was increased to 20 mg of potassium iodide per kilogram of salt. In 1994, further investigations in schoolchildren demonstrated an increase of urinary iodine excretion (121 microg/g Crea) and a reduction of goiter prevalence below 5%, with the exception of pupils ages 14-19 (12%). In the year 2000, 10 years after the increase of salt iodination in Austria, 430 nonselected adult inhabitants of three communities in Carinthia (a county of Austria) were investigated for iodine excretion, goiter prevalence, and prevalence of thyroid autoantibodies. This study demonstrated that although iodine supply is sufficient now in Austria (males, 163.7 microg of Crea; females, 183.3 microg of iodine per gram of Crea), goiter prevalence is still high in the elderly, who lived for a longer period of iodine deficiency (34.3% in women and 21.3% in men), whereas goiter prevalence in younger people up to age 40 years is below 5%. It could also be shown that the percentage of thyroid autoantibodies is now as high as in other countries with sufficient iodine supply (3.19% in males, 5.17% in females). In addition to the changes of urinary iodine excretion and goiter prevalence because of salt iodination, changes of incidence in hyperthyroidism and histologic types of thyroid cancer are discussed in this paper. In conclusion, the introduction of salt iodination led to an improvement in iodine supply with a marked reduction of goiter prevalence in people who were born after 1963, but also to an increase in hyperthyroidism and autoimmune thyroid diseases as well as changes in histologic types of thyroid cancer.

Value of ultrasound-guided fine-needle aspiration biopsy of thyroid nodules in an endemic goitre area.

Abstract.The aim of this study was to determine the value, advantages and limitations of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in an endemic goitre area. US-FNAB was performed on all outpatients who presented with hypoechoic and/or hypofunctional and/or growing nodules. A total of 4518 US-FNABs were performed and 718 patients from this series underwent surgery. Cytological results of the primarily performed US-FNAB of these patients were compared retrospectively with the histological results. US-FNAB results were grouped as (1) non-malignant (n=303), (2) non-malignant follicular proliferation (n=177), (3) malignancy cannot be ruled out (n=133), (4) malignant (n=61), (5) inadequate (n=34), and (6) sampling error; biopsy of a non-malignant nodule (n=10). Nodules as small as 5 mm in diameter could be biopsied, gaining representative material. US-FNAB found a malignant or suspicious cytology in 65 out of 87 cases with malignant histology (74.71%). Diagnosis of early tumour stages was often possible: 12 of 18 thyroid carcinomas biopsied and smaller than 10 mm in diameter had malignant or suspicious cytology (groups 3 and 4). US-FNAB was performed incorrectly within non-malignant nodules in ten patients (1.39%) with multinodular goitre (ten papillary carcinomas, nine smaller than 10 mm). Regarding the cytology of groups 1 and 2 as benign and those of groups 3 and 4 as malignant, US-FNAB performance was as follows: sensitivity 87.84%, specificity 78.50%, negative predictive values 98.13%, positive predictive values 33.51% and accuracy 79.53%. Biopsies with inadequate material were obtained in 4.73% of all biopsies. No major adverse effects occurred. Re-biopsies in 61 cases did not alter the cytological outcome in those cases where adequate material was obtained. US-FNAB is a valuable method in the pre-operative assessment of thyroid nodules in order to select patients for surgery, as malignancy can often be detected even in early tumour stages. However, even with ultrasonographic guidance, the minimal tumour size detectable by US-FNAB is around 5 mm. The cytological interpretation in cases with regression and microfollicular proliferation also sets limits on the method. However, patients with non-malignant cytologies can be followed up safely by sonography due to the high NPV of US-FNAB as long as thyroid nodules do not become larger. Re-biopsies seem to be of limited value as long as adequate material was obtained by US-FNAB.

18F-FDG positron emission tomography in the early diagnosis of enterocolitis: preliminary results

Abstract. Collagenous and eosinophilic colitis are rare diseases characterised by chronic watery diarrhoea. Radiographic evaluation of the gastrointestinal tract and colonoscopy are usually non-diagnostic since as many as one-third of patients will have minor abnormalities. To date a few investigators have reported increased fluorine-18 fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography (PET) in patients with acute enterocolitis, but there have been no reports on the use of 18F-FDG PET for the diagnosis of collagenous or eosinophilic colitis in an early clinical stage. The aim of this preliminary study was to evaluate the usefulness of 18F-FDG PET in the early diagnosis of patients with colitis. We investigated five women (mean age 61.2±12.1 years) who had been diagnosed as having colitis in an early clinical stage. In all but one of the patients, the diagnosis of colitis was based on biopsy. Magnetic resonance colonography, ultrasonography and colonoscopy were performed in all but one of the patients. Two women were identified as having collagenous colitis in an early clinical stage. Another two patients had eosinophilic colitis. The morphological imaging methods, magnetic resonance colonography and ultrasonography, yielded no suspicious findings, and the results of colonoscopy similarly showed no abnormalities. One patient had colitis due to bacterial infection. In all patients 18F-FDG PET showed a pathological increase in tracer uptake in the large bowel, suggestive of colitis. In four of the five patients, colitis was confirmed by histology, and in one, by bacterial analysis. 18F-FDG PET was able to detect colitis in an early clinical stage, when morphological imaging methods and colonoscopy were non-diagnostic. The early performance of 18F-FDG PET imaging in patients with possible colitis is encouraging.

Lymphoscintigraphy and Gamma probe-guided surgery in papillary thyroid carcinoma : The sentinel lymph node concept in thyroid carcinoma

The authors report the use of lymphoscintigraphy and gamma probe-guided resection of the sentinel lymph node in a 65-year-old woman with clinically and cytologically indicated metastasizing papillary thyroid carcinoma. The results of the preoperative lymphoscintigraphy corresponded well with FDG PET and histologic findings, which gives promise of its validity in thyroid carcinoma. With experience in ultrasound-guided fine-needle aspiration biopsy, this method can be performed without any serious side effects for the patient. The validity of the sentinel lymph node concept in thyroid carcinoma and a possible improvement of nodal staging and local recurrence rate must still be proved.

Technetium 99m tetrofosmin parathyroid imaging. Results with double-phase study and SPECT in primary and secondary hyperparathyroidism.

RATIONALE AND OBJECTIVES The aim of our study was to evaluate the sensitivity, specificity, and positive predictive value (PPV) of technetium 99m (99mTc) tetrofosmin double-phase scintigraphy and single-photon emission computer tomography (SPECT) in preoperative localization of parathyroid adenoma in case of primary and secondary hyperparathyroidism (HPT). METHODS Sixty-eight consecutive patients biochemically or sonographically suspected of parathyroid adenoma were included in our study. Apart from biochemical analysis of serum calcium, phosphate, and intact parathyroid hormone, double-phase scintigraphy was performed in each patient 5 and 45 minutes after injection of 370 MBq 99mTc tetrofosmin, followed by SPECT imaging. In consciousness of the scintigraphic results, ultrasound of the neck was performed as well to exclude false-positive results due to thyroid adenomas. RESULTS Depending on the results of the biochemical analysis in combination with the results of the scintigraphic and ultrasound examination, the patients were classified retrospectively into three groups: group A with primary HPT (n = 35), group B with secondary HPT (n = 13), and group C without any biochemical suspicion of primary or secondary HPT (n = 20). In group A, double-phase study localized 25 of 36 (69.2%) parathyroid adenomas (one double adenoma) as against 34 of 36 (94.4%) with SPECT. Nine adenomas could be visualized only by SPECT. The reason for nonvisualization on planar scans was suspected to be an ectopic location in 2 cases (retrotracheal dislocation, retrovascular dislocation), a maximal diameter less than 15 mm (9-13 mm) in 6 cases, and oxyphilic-cell-poor cellularity in 1 case. Four false-positive retention (3 thyroid adenomas and 1 papillary thyroid carcinoma) were observed. SPECT showed a sensitivity of 94.4%, a specificity of 85%, and a PPV of 91.9% in biochemically suspected primary HPT. In group B, planar scintigraphy demonstrated 12 hyperplastic glands in 5 of 13 patients, and SPECT demonstrated 20 hyperplastic parathyroid glands in 8 out of 13 patients, which corresponds to a sensitivity of 38% and 61.5%, respectively. CONCLUSIONS Technetium 99m tetrofosmin seems to be a promising alternative tracer with similar capabilities to 99mTc sestamibi in localization of parathyroid adenoma. SPECT showed clear advantages in terms of sensitivity over planar scintigraphy and should be used at least in cases with poor or no uptake in double-phase study. In endemic goiter areas, ultrasound of the neck should be performed to exclude false positive retention in thyroid adenomas. Technetium 99m tetrofosmin, like 99mTc sestamibi, is not ideal for localization of hyperplastic glands in secondary hyperparathyroidism because of low sensitivity.

Comparison between 99mTc-tetrofosmin/pertechnetate subtraction scintigraphy and 99mTc-tetrofosmin SPECT for preoperative localization of parathyroid adenoma in an endemic goiter area.

RATIONALE AND OBJECTIVES Technetium-99m-((99m)Tc-) tetrofosmin, a cationic, lipophilic complex like (99m)Tc-sestamibi, has proved to be a potential tracer for parathyroid scintigraphy despite some differences in washout behavior from the thyroid gland. Previous results comparing a double-phase technique with single-proton emission computed tomography (SPECT) or with subtraction techniques demonstrated a high detection rate, especially when SPECT and subtraction techniques were used, whereas the double-phase protocol revealed only moderate results. In this study, a direct comparison was made between (99m)Tc-tetrofosmin/pertechnetate subtraction and SPECT to elucidate the optimal protocol for tetrofosmin parathyroid imaging. METHODS Twenty-three patients who were biochemically suspected of parathyroid adenoma or hyperplasia due to primary or tertiary hyperparathyroidism were included in our study. In all patients, serum calcium, phosphate, and intact parathormone levels were analyzed in a single blood sample before (99m)Tc-tetrofosmin/pertechnetate subtraction scintigraphy and SPECT. Ultrasound of the neck was performed in all patients to exclude false-positive results due to thyroid adenomas. All patients underwent parathyroidectomy with intraoperative revision of all parathyroid glands, and the histological results were compared with preoperative findings. RESULTS Both imaging modalities, ie, subtraction scintigraphy and SPECT, correctly identified 20 of 23 (87%) histologically confirmed adenomas preoperatively. The positive predictive value was calculated to be 95% and 100%, respectively, for these two methods. Subtraction scintigraphy and SPECT showed concordant results in 19 patients (18 positive, 1 false-negative) and discordant results in 4 patients (2 positive with subtraction, 2 with SPECT). The combined use of subtraction scintigraphy and SPECT techniques revealed a sensitivity of 95.7% (22/23) and a positive predictive value of 95%. The whole procedure can be performed in less than 90 minutes per patient. Whereas subtraction scintigraphy tended to show more false-positive retentions due to thyroid adenomas, the interpretation of SPECT may be difficult in small adenomas with missing thyroid/parathyroid differential washout. CONCLUSIONS Both imaging modalities, subtraction scintigraphy with pertechnetate and SPECT, are highly sensitive methods for parathyroid adenoma localization with (99m)Tc-tetrofosmin. However, our study did demonstrate that a combination of both modalities can further improve the diagnostic accuracy. Especially in an endemic goiter area, additional ultrasound may be required to avoid false-positive results due to thyroid adenomas.

Goiter Prevalence and Urinary Iodide Excretion in a Formerly Iodine-Deficient Region After Introduction of Statutory Iodization of Common Salt

The objective of this epidemiologic study was to determine the volume of the thyroid gland as well as urinary iodine excretion in dependence on age and gender in a population from an area of low natural iodine supply now receiving iodine prophylaxis. In 430 persons from three communities in the province of Carinthia, Austria, we determined thyroid volume via sonography as well as urinary iodide excretion. As in numerous other European countries, natural iodine supply is insufficient in Austria. Therefore, to reduce goiter incidence, iodization of common salt with 10 mg potassium iodide (KI) per kilogram of NaCl was made mandatory in Austria in 1963 by federal law. In 1990, the amount of iodine addition was increased to 20 mg KI per kilogram of NaCl. Our results show that mean urinary iodide excretion in the persons investigated was altogether satisfactory (males: 163.7 microg of iodine per gram of creatinine; females: 183.3 microg of iodine per gram of creatinine). Goiter prevalence was 34.3% in women and 21.3% in men. An increase in goiter occurrence with age was noted in both genders. The increase in goiter prevalence was particularly obvious in the age group older than 40, i.e., among those participants who had spent at least a certain span of their lives in an area of iodine deficiency. Thus, the most likely reason for the persistently high goiter prevalence is not current iodine deficit but rather the high number of goiters that had developed previously at the time of iodine deficiency and were unable to undergo regression in spite of todays comparatively good iodine supply situation.

Bone Metabolism in Patients with Differentiated Thyroid Carcinoma Receiving Suppressive Levothyroxine Treatment

AIM Patients with differentiated thyroid carcinoma (DTC) must receive suppressive levothyroxine (LT(4)) therapy for the rest of their lives. The literature, however, presents conflicting results on how this affects bone metabolism. The aim of this study was to assess the influence of the estrogen status and LT(4) therapy, in particular LT(4) dosage in micrograms per kilograms (microg/kg), on bone metabolism in female patients with DTC. MATERIAL AND METHODS Three markers of bone metabolism (C-terminal telopeptide of type I collagen in serum [SCTx]; N-terminal telopeptide of type I collagen in urine [U-NTx]; and osteocalcin [OC]) were investigated in four groups: group REF (healthy premenopausal female controls), group DTC-ES (premenopausal women with DTC and normal estrogen levels), group DTC-ED (postmenopausal women with DTC and estrogen deficiency), and group DTC-HRT (postmenopausal women with DTC undergoing hormone replacement therapy [HRT]). All patients with DTC were on a well-adjusted suppressive LT(4) therapy with TSH levels 0.1 mU/L or less. RESULTS In group DTC-ES bone turnover was comparable to group REF, whereas in group DTC-ED, all three markers were significantly increased as compared to groups REF and DTC-ES. In group DTC-HRT, the HRT normalized U-NTx and OC. However, in this group S-CTx was not completely normalized by HRT in all patients, although also significantly lowered compared to group DTC-ED. The analysis of LT(4 )dosage per kilogram showed that premenopausal DTC-patients had increased markers of bone metabolism if LT(4) dosage exceeded 2.6 microg/kg. Estrogen-deficient patients with DTC, however, had a much lower critical LT(4) dosage, above which increased markers of bone metabolism were seen. CONCLUSION A well-adjusted suppressive LT(4) therapy of less than 2.6 microg/kg and normal estrogen levels do not seem to increase bone metabolism in estrogen-sufficient patients with DTC. The normalization of an estrogen deficiency by HRT or other antiresorptive therapies and minimal suppressive dosages of LT(4) are attempts to optimize the care of patients with DTC. In postmenopausal patients with DTC and patients with DTC who require LT(4) dosages in excess of 2.6 microg/kg, the information provided by markers of bone metabolism may help to prevent bone damage.