[Fine-needle aspiration (FNA) of the thyroid gland : Analysis of discrepancies between cytological and histological diagnoses]. / Feinnadelaspiration (FNA) der Schilddrüse : Analyse diskrepanter zytologischer und histologischer Diagnosen.

BACKGROUND: Diagnostic problems of thyroid cytology are frequently discussed, but relevance and causes of discrepant cytological and histological diagnoses are rarely studied in detail. OBJECTIVES: Investigation of causes and relevance of discrepant diagnoses. MATERIALS AND METHOD: The analysis includes 297 patients who had thyroid resection after prior fine needle aspiration (FNA) and is based on the cytological and histological reports. In special cases, cytological and histological specimens were re-examined. RESULTS: Malignant tumors were found in 45 patients (15.1 %). In 5 patients the cytological diagnosis was "false negative". Three of these 5 tumors were papillary carcinomas (PTC) of ≤10 mm, one an obviously nonmalignant papillary proliferation of the thyroidal epithelium and one a malignant lymphoma complicating autoimmune thyreoiditis (AIT). In 11 of the 35 patients with a FNA diagnosis "suspicious of malignancy" or "malignant," 1 AIT, 4 goiter nodules, and 6 adenomas were diagnosed histologically. However, since distinct nuclear atypia was found in three of five false positive diagnoses, there still remains doubt in their benignity. CONCLUSIONS: Carcinomas of ≤10 mm incidentally detected in the resected thyroid tissue may not be relevant to the patient and do not reduce the high negative predictive value of FNA. The final diagnosis on the resected tissue should include the cytological findings. Discrepant findings should be commented in the report to the clinician.

Salivary gland protection by amifostine in high-dose radioiodine treatment: results of a double-blind placebo-controlled study.

PURPOSE: Salivary gland impairment is a well-recognized side effect following high-dose radioiodine treatment (HD-RIT). Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. Therefore, the effect of amifostine was studied in HD-RIT. PATIENTS AND METHODS: Parenchymal function was assessed by quantitative salivary gland scintigraphy performed prospectively in 50 patients with differentiated thyroid cancer before and 3 months after HD-RIT with either 3 GBq iodine ((131)I) (n=21) or 6 GBq (131)I (n=29) in a double-blind, placebo-controlled study. Twenty-five patients were treated with 500 mg/m2 amifostine intravenously before HD-RIT and 25 patients served as controls, who received physiologic saline solution. Xerostomia was graded according to World Health Organization (WHO) criteria. RESULTS: Before HD-RIT in 25 control patients, uptake of technetium-99m (99mTc)-pertechnetate was 0.45%+/-0.16% and 0.42%+/-0.16% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function was significantly (P < .001) reduced by 40.2%+/-14.1% and 39.9%+/-15.3% in parotid and submandibular glands, respectively. Nine control patients developed grade I and two grade II xerostomia. In 25 amifostine-treated patients, uptake of 99mTc-pertechnetate was 0.46%+/-0.16% and 0.43%+/-0.17% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function of salivary glands was not significantly altered (P=.691) and xerostomia did not occur in any of these patients. CONCLUSION: Parenchymal damage in salivary glands caused by HD-RIT can significantly be reduced by amifostine, which may improve the quality of life of patients with differentiated thyroid cancer.

Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model.

BACKGROUND: Impairment of salivary gland function following high-dose radioiodine treatment (HDRIT) is a well-recognized side effect of the treatment. Because differentiated thyroid cancer has an excellent prognosis, reduction of long-term side-effects is mandatory. Therefore, the aim of this study was to investigate the radioprotective effect of amifostine in a rabbit animal model. METHODS: Salivary gland scintigraphy was performed in a total of 16 New Zealand White rabbits. Uptake of 99-Tc-pertechnetate was calculated in percentage of injected activity as a quantitative measure of both salivary gland and thyroid function. Reproducibility of salivary gland scintigraphy was evaluated in one rabbit without any intervention. Fifteen rabbits were studied prior to and up to 6 months after high-dose radioiodine treatment applying 2 GBq 131I. Ten animals received 200 mg/kg amifostine prior to high-dose radioiodine therapy, and 5 served as controls. Salivary glands were examined histopathologically. RESULTS: Variation coefficient of parenchymal function was less than 3.8% in salivary glands. Prior to HDRIT, thyroid uptake was 0.417+/-0.373% and 0.421+/-0.241% in control and amifostine-treated rabbits, respectively. Four weeks after HDRIT, complete ablation of the thyroid was achieved in both groups. Prior to HDRIT, uptake of 99mTc-pertechnetate in salivary glands of five control rabbits was not significantly different from ten amifostine-treated rabbits. In control rabbits 6 months after HDRIT, parenchymal function was reduced significantly (p < 0.0001) by 75.3+/-5.3% and 53.6+/-17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits, parenchymal function was reduced by 10.6+/-3.4% and 6.5+/-4.3% (p > 0.05) in parotid and submandibular glands, respectively. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. CONCLUSION: Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine in this rabbit animal model. This corresponds to data obtained in patients with differentiated thyroid cancer.

Quality assurance in PET: evaluation of the clinical relevance of detector defects.

UNLABELLED: Defective detector blocks in PET may cause serious image artifacts. To estimate the influence of malfunctioning detectors on image quality, a method is described for transferring the actual detector defect onto previously acquired scans. METHODS: Consequences of detector defects of varying types and extensions were simulated in phantom studies as well as in clinical 18F-fluorodeoxyglucose investigations. First, a condition frame was obtained by dividing the sinogram of a blank measurement, obtained with rod sources on the defective PET camera, by the sinogram of a reference blank acquired before the appearance of the defect. Second, the sinogram of a previously acquired typical patient study was multiplied by the condition frame and reconstructed. Thereafter, images from corrupted sinograms were compared visually with their originals. For repairing defective sinograms, linear interpolation and the constrained Fourier space method were tested. RESULTS: The effects of detector defects can be simulated accurately in patient studies. The correction methods applied are especially helpful in cases of (a) several neighboring defective detectors and small study objects, (b) small hot artifacts and (c) several nonadjacent defective detectors. Linear interpolation is faster than the constrained Fourier space method; it is more widely applicable and provides similar results. CONCLUSION: The proposed approach allows specific evaluation of clinical consequences of detector defects. This technique simplifies the decision as to whether a planned patient study can be performed or must be postponed. Even in cases of serious detector problems, sinogram repair may help eliminate image artifacts and minimize the loss of image quality.

Molecular biologic and scintigraphic analyses of somatostatin receptor-negative meningiomas.

UNLABELLED: Somatostatin receptor scintigraphy (SRS) using 111In-octreotide has proven useful in the preoperative discrimination of expansive central nervous system lesions. Meningiomas, generally expressing human somatostatin receptor (hsst) on their surface, were detected with a sensitivity of about 100%. This finding was associated with the assumption that meningiomas lack an intact blood-brain barrier. However, this exclusion procedure became questionable when histologically proven meningiomas in which SRS was negative were reported. Therefore, the aim of this study was to discover why these meningiomas gave negative SRS results. METHODS: Before surgery, 46 patients with 47 meningiomas underwent standard MRI and SRS. Thirty-four of these patients with 35 tumors were also examined by 99mTc-diethylenetriaminepentaacetic acid (DTPA) brain scintigraphy. After surgical resection, hsst subtype 2 (hsst2) messenger RNA (mRNA) expression of 4 SRS-positive and 4 SRS-negative meningiomas was estimated semiquantitatively by reverse transcriptase polymerase chain reaction (RT-PCR). Translation of hsst2 mRNA into receptor proteins was proven immunocytochemically on the surface of 1 SRS-positive and 1 SRS-negative meningioma. Tumor specimens used for RNA extraction and RT-PCR and cultivated cells used for hsst2 immunostaining were tested for their meningioma nature by immunochemistry. RESULTS: SRS yielded positive results in 39 meningiomas with a tumor volume of 24.1 +/- 32.8 mL and negative results in 8 meningiomas with a volume of 3.9 +/- 6.5 mL. 99mTc-DTPA scintigraphy visualized 24 of 35 meningiomas. SRS was positive in all of them. In contrast, 11 meningiomas were (99mTc-DTPA negative. In these meningiomas, SRS was negative in 5 cases (5.4 +/- 8.1 mL), whereas the remaining 6 were positive (4.6 +/- 4.5 mL). None of the meningiomas was 99mTc-DTPA positive and SRS negative. RT-PCR revealed no significant difference of hsst2 mRNA expression between SRS-positive and SRS-negative meningiomas but showed varied expression among all meningiomas regardless of SRS results. Furthermore, hsst2 proteins were visualized immunocytochemically on the surface of cultivated cells of SRS-positive and SRS-negative meningiomas. CONCLUSION: SRS-negative meningiomas do express hsst2; thus, in these meningiomas SRS is false-negative. Because an insufficient sensitivity was excluded, 99mTc-DTPA scintigraphy identified a permeability barrier in SRS-negative meningiomas that explains their false-negative SRS results. SRS-negative meningiomas most likely meet the function of their tissue of origin (the meninges) to develop more-or-less intact permeability barriers.

In vitro and in vivo tracer characteristics of an established multidrug-resistant human colon cancer cell line.

UNLABELLED: 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) has been suggested as a tracer for the scintigraphic detection of multidrug resistance (MDR). The aim of this study was to compare MDR characteristics in vitro and in vivo by immunohistochemic and functional uptake assays in established tumor cell lines cultured and grown in severe combined immunodeficient (SCID) mice. METHODS: The presence of MDR was assessed in vitro in drug-resistant HT-29(mdr1) colon carcinoma cells and in nonresistant HT-29(par) cells by JSB-1 immunohistochemistry, uptake of the fluorescent dye Rhodamine 123, and quantitative measurement of 99mTc-MIBI accumulation. For in vivo imaging, SCID mice bearing subcutaneous xenografts of these cell lines were injected with 99mTc-MIBI and 18F-FDG for scintigraphic and PET examination. After imaging, tumors were analyzed by immunohistochemistry and electron microscopy. RESULTS: All HT-29(mdr1) cells cultured in vitro exhibited distinct JSB-1 immunoreactivity, although to a variable degree, whereas HT-29(par) cells were completely devoid of JSB-1 staining. Rhodamine 123 accumulated poorly in HT-29(mdr1) cells but strongly in HT-29(par) cells. Accumulation of 99mTc-MIBI was 0.05% +/- 0.01% of the activity of the external medium in HT-29(mdr1) cells, but about eight times higher in HT-29(par) cells (0.40% +/- 0.09%), a very low percentage compared with other tumor cell lines. No difference in 201TlCl accumulation was observed between both cell lines. In vivo, neither HT-29(par) nor HT-29(mdr1) tumors grown in SCID mice could be detected by 99mTc-MIBI scintigraphy. In FDG PET, both HT-29(mdr1) and HT-29(par) tumors were clearly visible. FDG uptake was, however, markedly higher in HT-29(par) than in HT-29(mdr1) tumors. Both tumor types were poorly vascularized, as shown histologically. JSB-1 immunoreactivity was absent in all HT-29(par) tumors examined, whereas the majority of HT-29(par) tumor cells were stained. Electron microscopy showed that HT-29(par) tumors contained significantly less mitochondria than hepatocytes of the SCID mouse liver, which displayed high 99mTc-MIBI uptake in our scintigraphy studies. CONCLUSION: Sufficient 99mTc-MIBI uptake is the major prerequisite for distinguishing successfully between drug-resistant and sensitive cells. Negative 99mTc-MIBI scintigrams are not necessarily associated with MDR expression. In some tumors, FDG may be an in vivo marker for MDR as suggested by PET.

Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan.

UNLABELLED: FDG PET is increasingly performed in patients with differentiated thyroid cancer who present with elevated human thyroglobulin (hTG) levels and negative 131I scan. The aim of this study was to evaluate the impact of FDG PET on treatment in these patients. METHODS: A total of 118 FDG PET studies were performed on 64 patients, and follow-up data were available for all patients. Whole-body images were acquired 1 h after intravenous injection of 370 MBq (10 mCi) FDG using a PET scanner with an axial field of view of 16.2 cm. Tumor-suspicious FDG PET studies were evaluated by histology, cytology, 131I uptake, CT or MRI, and follow-up of hTg levels. The therapeutic consequence was noted for each patient. Moreover, results of FDG PET were correlated with hTg levels. RESULTS: Forty-four patients had positive scans, which were proven to be true-positive in 34 patients, whereas 7 patients had false-positive findings. Two patients exhibited a secondary malignancy. One patient did not fit in any category, having true-positive, false-positive, and false-negative findings. On the other hand, 20 patients had negative scans. These were true-negative findings in 5 patients, whereas the remaining 15 patients had false-negative results. Accordingly, the positive predictive value of FDG PET was 83% (34/41), whereas the negative predictive value was 25% (5/20). Treatment was directly changed in 19 of 34 patients with true-positive PET studies: 18 patients had further surgery, and 4 patients were referred for external irradiation, 3 of them after incomplete removal of local recurrences. FDG PET showed widespread disease in 7 patients; thus, palliative treatment, rather than curative therapy, was initiated. True-positive FDG PET findings were correlated positively with increasing hTg levels (i.e., FDG PET was true-positive in 11%, 50%, and 93% of patients with hTg levels of <10, 10-20, and >100 microg/L, respectively). CONCLUSION: FDG PET is a valuable diagnostic tool in patients with differentiated thyroid cancer who present with increased hTg levels and negative 131I scans because it permits selection of patients for surgery, which may be curative. FDG PET is most promising at hTg levels of >10 microg/L.

FDG PET detection of unknown primary tumors.

UNLABELLED: The management of patients presenting with metastases of unknown primary origin remains a clinical challenge despite a large variety of imaging modalities. The aim of this study was to evaluate FDG PET in detecting the sites of primary cancer in these patients. METHODS: Fifty-three patients with metastatic cervical adenopathy (n = 44) or extracervical metastases (n = 9) of unknown primary origin were included after extensive but inconclusive conventional diagnostic work-up. Patients received 370 MBq FDG (10 mCi) intravenously, and whole-body images were acquired at 60 min after injection. Clinical, surgical, and histopathologic findings and complete correlative imaging were used to assess the results. RESULTS: In 27 of 53 patients FDG PET showed focal tracer accumulations corresponding to potential primary tumor sites located in the lungs (n = 12), the palatine tonsil (n = 5), the salivary glands (n = 2), the nasopharynx (n = 1), the oropharynx (n = 3), the maxillary sinus (n = 1), and the larynx (n = 1). Moreover, in 2 patients FDG PET revealed lesions suspected to be tumors in the breast and the ileocolonic area. In 20 (37.8%) of these 53 patients FDG PET was true-positive, identifying the primary tumor in the lungs (n = 10), the head and neck region (n = 8), the breast (n = 1), and the ileocolonic area (n = 1). In 6 of 27 patients FDG PET was false-positive, predominantly identifying suspicious areas in the palatine tonsil (n = 3). One patient denied further diagnostic work-up after PET; thus, positive PET could not be evaluated. In 26 of 53 patients PET did not reveal lesions suspected to be the primary. However, primary tumors were not found in these patients at clinical follow-up. CONCLUSION: FDG PET is a valuable diagnostic tool in patients with cancer of unknown primary because it imaged unknown primary tumors in about one third of all patients investigated. In addition, FDG PET assists in both guiding biopsies for histologic evaluation and selecting the appropriate treatment protocols for these patients.

Clinical value of 24-hour delayed imaging in somatostatin receptor scintigraphy for meningioma.

UNLABELLED: Somatostatin receptor scintigraphy (SRS) using 111In-octreotide has proven useful in patients suspected of having meningiomas. Delayed imaging is regularly performed up to 24 h postinjection. However, this procedure is time consuming and expensive. Therefore, we investigated whether 24-h imaging may be omitted in these patients. METHODS: After clinical examination and standard MRI, 71 patients were suspected of having 92 meningioma lesions. Before surgery, all patients underwent SRS after intravenous injection of 200 MBq (5.4 mCi) 111In-octreotide. Planar whole-body images were obtained at 10 min and 1, 4 and 24 h, and SPECT was performed at 4 and 24 h. Results of SRS in all lesions were evaluated with respect to histology and time of image acquisition. RESULTS: SRS yielded 58 true-positive, 20 true-negative and 14 false-negative results, with the false-negatives all less than 5 mL (2.3+/-2.1 mL) in volume. In 52 of 58 true-positive lesions (89.7%), diagnosis could be established by 4-h imaging without further information by 24-h imaging. In 10 of the 52 lesions, SPECT was necessary to confirm planar findings. Imaging at 24 h was necessary in only 6 of 58 true-positive lesions (10.3%): 3 patients who had intracranial relapse of meningioma (volume < 5 mL) and 3 who had spinal meningioma. Thus, a diagnosis of intracranial meningioma could be established in 52 of 55 lesions (95%) using a 4-h imaging protocol. CONCLUSION: With a 4-h acquisition protocol that includes SPECT imaging, SRS yields sufficient information in patients suspected of having intracranial meningiomas. Delayed imaging at 24 h is recommended only for patients who have small meningiomas (volume < 5 mL), spinal localizations or negative SRS at 4 h.

Somatostatin receptor scintigraphy in postsurgical follow-up examinations of meningioma.

UNLABELLED: Surgery is the treatment of choice in patients with meningioma. However, the risk of postoperative, local recurrence is well-known since total resection is not always feasible. Moreover, in these patients MRI may fail to differentiate between tumor remnants, recurrent meningioma or nonspecific hyperperfusion. In this study, the value of functional imaging using somatostatin receptor scintigraphy (SRS) was evaluated in postsurgical follow-up. METHODS: Before and 2-3 mo after surgery, 27 patients with meningioma received MRI as well as SRS after intravenous injection of 200 MBq 111In-octreotide. Planar whole-body images were obtained at 10 min, 1, 4 and 24 hr postinjection, and SPECT was performed at 4 and 24 hr postinjection. The final diagnosis was proven histologically in all patients. RESULTS: Before surgery, MRI showed focal contrast enhancement in all patients, and SRS revealed focal accumulation of 111In-octreotide. Thus, MRI and SRS yielded comparable results in all 27 patients. After surgery, MRI showed diffuse contrast enhancement in the area of the primary tumor site in all patients. Thus, MRI did not allow a differentiation between tumor and nonspecific hyperperfusion. In contrast, SRS revealed focal accumulation of 111In-octreotide in 16 of 27 patients indicating remaining tumor tissue or relapse of meningioma. This resulted either in an operative revision or in more frequent postsurgical follow-up examinations. In 11 of 27 patients, SRS was negative. Thus, total resection of meningioma was assumed, and no further interventions were performed. CONCLUSION: Functional imaging using SRS is a highly specific imaging modality and has a significant impact in postsurgical follow-up in patients with meningioma.

Radioprotection of salivary glands by amifostine in high-dose radioiodine therapy.

UNLABELLED: Salivary gland impairment after high-dose radioiodine treatment is well recognized. Because differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. This study investigated the radioprotective effects of amifostine in animals and humans receiving high-dose radioiodine therapy. METHODS: Quantitative salivary gland scintigraphy was performed in five rabbits before and up to 3 mo after high-dose radioiodine therapy applying 1 GBq 131I. Three animals received 200 mg/kg amifostine before high-dose radioiodine therapy, and two served as controls. All animals were examined histopathologically. Quantitative salivary gland scintigraphy also was performed in 17 patients with differentiated thyroid cancer before and 3 mo after high-dose radioiodine therapy with 6 GBq 131I. Eight patients were treated with 500 mg/m2 amifostine before high-dose radioiodine therapy, and nine served as controls. RESULTS: In two control rabbits, high-dose radioiodine therapy significantly reduced parenchymal function by 63% and 46% in parotid and submandibular glands, respectively. In contrast, there was no significant decrease in parenchymal function in amifostine-treated animals. Histopathologically, lipomatosis was observed in control animals but was negligible in amifostine-treated animals. Similar findings were observed in differentiated thyroid cancer patients. In nine control patients, high-dose radioiodine therapy significantly (p < 0.01) reduced parenchymal function by 37% and 31% in parotid and submandibular glands, respectively. Three patients exhibited Grade I (World Health Organization) xerostomia. In contrast, there was no significant decrease in parenchymal function in amifostine-treated patients and no incidence of xerostomia. CONCLUSION: Parenchymal damage in salivary glands induced by high-dose radioiodine therapy can be reduced significantly by amifostine. This may increase the quality of life of patients with differentiated thyroid cancer.

Ventilation scintigraphy of the middle ear.

UNLABELLED: In this study, an attempt was made to administer radioactive gas into the tympanic cavity to measure initial gas trappings as well as clearance from the middle ear to evaluate eustachian tube function. METHODS: Twenty-eight patients were administered 50 MBq 133Xe gas. Three different methods for gas application were tested: (a) direct injection through a tympanostomy tube in two patients, (b) administration through a nasopharyngeal catheter combined with Valsalva maneuvers in six subjects without middle ear dysfunction and (c) insufflation into the pharyngeal space through a nose olive performed in 12 patients with normal eustachian tube function and in eight patients with one-sided tube dysfunction. RESULTS: All three approaches were successful in visualizing middle ear ventilation, demonstrating tracer trapping within the tympanic cavities in 20 of 28 patients. Semiquantitative evaluation by region of interest techniques revealed a left-to-right uptake ratio of 48.4%-51.6% in 13 patients without tube dysfunction. Five patients with one-sided tube dysfunction showed a significantly lower median uptake of 31.6% (p = 0.01). The clearance half-lives ranged from 9 to 283 min in normal subjects and 37-64 min in patients with one-sided tube malfunction, demonstrating no statistically significant difference between the two groups and a trend towards increased washout in patients with tympanic dysfunction. CONCLUSION: Middle ear ventilation scintigraphy with 133Xe through a nose olive is an easy-to-perform test to evaluate eustachian tube function and has a success rate of about 70%, thus, reflecting the complex physiological mechanisms involved.

Lymphoscintigraphy in tumors of the head and neck using double tracer technique.

UNLABELLED: Knowledge of possible lymphatic drainage may facilitate planning of surgery for patients with head and neck tumors. Therefore, the aim of this study was to present a method of lymphoscintigraphy with special attention to an accurate correlation of lymphatic drainage to anatomic regions. METHODS: Lymphoscintigraphy was performed using a double tracer technique before surgery in a total of 75 patients with squamous cell carcinoma of the head and neck. All patients received 100 MBq 99mTc-colloid at three to four peritumoral sites. A perchlorate solution (2 mL) was given orally to block salivary glands and the thyroid gland. Patients received 50 MBq 99mTc-pertechnetate intravenously for body contouring 20 min postinjection. Planar images were obtained over 5 min each, at 30 min and 4 h postinjection from anterior, right lateral and left lateral views with a large-field-of-view gamma camera. Lymphatic drainage was assessed by visual inspection and assigned to six cervical compartments. RESULTS: Neither the salivary glands nor the thyroid gland were seen in any of the patients. In 22 of 75 patients (29.3%), the injection site was the only focal tracer uptake seen. In contrast, lymphatic drainage was identified in the remaining 53 patients (70.7%), and lymph nodes could be assigned easily to the six cervical compartments. Of 75 patients, 36 (48%) exhibited ipsilateral lymphatic drainage. In addition, 17 patients (22.7%) with unilateral tumor showed bilateral (n = 12), contralateral (n = 2) or retropharyngeal (n = 3) lymphatic drainage. In 3 of these 17 patients, bilateral lymph node metastases were proven. A subgroup of 12 patients (16%) exhibited N2c nodal status, despite a unilateral localized primary tumor. In 3 of these 12 patients, surgery was extended as a result of scintigraphic findings from unilateral toward bilateral neck dissection, and histology confirmed nodal involvement in these patients. CONCLUSION: Lymphoscintigraphy using the double tracer technique allows an accurate correlation of lymphatic drainage to the six cervical compartments. This may provide the basis for a re-evaluation of its impact in treatment planning of patients with head and neck tumors.

Effect of attenuation correction on lesion detectability in FDG PET of breast cancer.

UNLABELLED: The aim of this study was to compare the visual analysis of attenuation-corrected and noncorrected 18F-fluoro-2-deoxy-D-glucose (FDG) PET images in patients with primary or metastatic breast cancer using standardized film documentation and to evaluate the influence of attenuation correction on lesion detectability. METHODS: Standard FDG PET of the breasts and of the axillary regions was performed on 28 women with breast cancer. Transmission scans were acquired for attenuation correction after administration of FDG. Transverse and coronal slices and maximum intensity projections both with and without attenuation correction were documented in a standardized manner on film. Noncorrected images were displayed with an upper threshold of five times the mean activity in normal lung tissue. Attenuation-corrected images were documented with an upper threshold of a standardized uptake value of five. Two independent nuclear medicine physicians, who were unaware of the results of clinical investigation, other imaging modalities and histopathologic findings, interpreted the images visually, noncorrected images first. RESULTS: One hundred eighty-four of 189 lesions in 28 of 28 patients were found on attenuation-corrected and noncorrected images. Seventeen lesions were found in the breasts of 12 patients. In 18 patients, 31 axillary lesions were found. Moreover, 141 lesions representing distant metastases were detected in 18 patients. Attenuation-corrected images showed the same lesions in all patients but 2, in whom 5 of 189 small pulmonary lesions (2.6%) were not detected. Iterative reconstruction did not improve detectability of these lesions on attenuation-corrected images. These lesions were confirmed by CT, which revealed diameters of <1 cm. CONCLUSION: Attenuation correction by transmission measurement after injection may impair lesion detectability in PET for staging of breast cancer patients. When using the image modalities described, noncorrected PET images should be considered in image analysis.

Positron emission tomography in the staging of small-cell lung cancer : a preliminary study.

STUDY OBJECTIVES: Small-cell lung cancer (SCLC) has an unfavorable prognosis, especially when the disease is extensive at presentation. Accurate staging procedures are therefore needed for treatment planning. Positron emission tomography (PET) is a modern noninvasive imaging technique, the value of which for the staging of SCLC was investigated in the present study. SETTING: University hospital. PATIENTS: Thirty-one patients with suspected lung cancer were investigated for staging purposes using chest radiography, CT of the thorax and abdomen, abdominal ultrasound, and bone scanning. Twenty-five patients also received PET examinations during the staging procedures. Five of these patients were found to have SCLC, while two patients had mixed lesion types. Further analysis of the latter group was carried out. RESULTS: PET detected the primary tumor in all patients, and lymph nodes in five patients. All lymph nodes were proved to be malignant by endoscopic ultrasonography-guided fine-needle aspiration. Only one patient had distant metastases, which were detected by both CT and PET. CONCLUSIONS: PET appears be a suitable imaging method in SCLC. A potential role for the technique as a standard staging procedure will need to be tested by investigating a larger number of patients in a prospective study.

Salivary gland protection by S-2-(3-aminopropylamino)-ethylphosphorothioic acid (amifostine) in high-dose radioiodine treatment: results obtained in a rabbit animal model and in a double-blind multi-arm trial.

Since differentiated thyroid cancer has an excellent prognosis, reduction of long-term side effects of high-dose radioiodine treatment (HD-RIT), i.e. salivary gland impairment is important. Thus, radioprotective effects of amifostine were studied. Salivary gland function was quantified by scintigraphy both in rabbits and patients. Fifteen rabbits were studied prior to and up to 6 months after HD-RIT applying 2 GBq 131I. Ten animals received 200 mg/kg amifostine prior to HD-RIT, and five served as controls. Animals were examined histopathologically. Fifty patients with differentiated thyroid cancer were evaluated prospectively prior to and 3 months after HD-RIT with either 3 or 6 GBq 131I in a double-blind, placebo-controlled study. Twenty-five patients were treated with 500 mg/m2 amifostine intravenously prior to HD-RIT, and 25 patients receiving physiological saline solution served as controls. Complete ablation of the thyroid was achieved in all rabbits four weeks after HD-RIT. In control rabbits 6 months after HD-RIT parenchymal function was reduced significantly (p < 0.0001) by 75.3 +/- 5.3% and 53.6 +/- 17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits parenchymal function was not significantly reduced. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. In control patients, salivary gland function was significantly (p < 0.001) reduced by 40.2 +/- 14.1% and 39.9 +/- 15.3% in parotid and submandibular glands, respectively, three months after HD-RIT, and 11 patients developed xerostomia. In 25 amifostine-treated patients, salivary gland function was not significantly reduced (p = 0.691), and xerostomia did not occur. Thus, parenchymal damage in salivary glands induced by high-dose radioiodine therapy can be reduced significantly by amifostine. This may improve quality of life of patients with differentiated thyroid cancer.

Evaluation of chemiluminescence immunoassays for detecting thyroglobulin (Tg) and thyroid peroxidase (TPO) autoantibodies using the IMMULITE 2000 system.

The chemiluminescence assays for detection of autoantibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg) implemented on the IMMULITE 2000 system (Diagnostic Products Corporation) were evaluated. These were immunometric assays with antigen-coated beads and monoclonal murine anti-IgG antibodies conjugated with alkaline phosphatase. Precision was satisfactory with an intraassay precision of 5.3-5.5% for anti-Tg and 4.8-5.3% for anti-TPO and an interassay precision of 5.7-7.3% for anti-TPO and 5.2-7.5% for anti-Tg. The lower detection limit was determined as 5 IU/ml for anti-TPO and 2.2 IU/ml for anti-Tg. The average dilution linearities of 102% for anti-TPO and 100% for anti-Tg and the average recovery of 80-127% for anti-TPO and 93-112% for anti-Tg were acceptable. The findings of the tests were compared with the systems from Pharmacia & Upjohn, ORGenTec, Roche Diagnostics, Byk Sangtec Diagnostica and BRAHMS Diagnostica. Taking the respective cutoff value into account, concordance was 87-96% for anti-Tg and 87-97% for anti-TPO. Summarizing all results from the different methods revealed a clinical agreement of 95% for anti-TPO and 93% for anti-Tg. A good agreement was found with the IMMULITE anti-TPO and anti-Tg assays, which are closely related as regards method and biochemistry. Regression analysis gave the following results: anti-TPO IMMULITE 2000 vs anti-TPO IMMULITE: anti-TPO IMMULITE 2000 = 0.99 x IMMULITE anti-TPO - 1.43 IU/ml (r = 0.99, n = 144). anti-Tg IMMULITE 2000 vs anti-Tg IMMULITE: anti-Tg IMMULITE 2000 = 0.98 x IMMULITE anti-Tg + 1.63 IU/ml (r = 0.99, n = 86). Further age-dependent normal ranges were evaluated. A higher prevalence of elevated autoantibody titers was found for patients older than 50 years. The rate of elevated antibody titer can be reduced by using an age-dependent reference range: < or = 50 years anti-TPO < 35 IU/ml, anti-Tg < 40 IU/ml and > 50 years anti-TPO < 100 IU/ml, anti-Tg < 80 IU/ml. Further samples from clinically diagnosed Hashimoto's thyroiditis and Graves' disease were investigated. The levels of positive anti-Tg values and anti-TPO values accorded with those stated in the literature and were comparable to those measured with a reference assay. In the tested INSTAND e. V. interlaboratory samples there was high-level accordance with the expected clinical results.

[A search for the focus in patients with fever of unknown origin: is positron-emission tomography with F-18-fluorodeoxyglucose helpful?]. / Fokussuche bei Patienten mit Fieber unklarer Genese: ist die Positronen-Emissions-Tomographie mit F-18-Fluordesoxyglukose hilfreich?

PURPOSE: Search for focus in patients with fever of unknown origin (FUO). MATERIAL AND METHODS: In four patients with the above mentioned problem, F-18-FDG-PET was performed, following the common imaging methods, which were without evidence for a focus. RESULTS: The origin of FUO was verified in all patients by PET: Tuberculosis, pneumocystis-carinii pneumonia, chronic inflammatory hematoma, aortitis. CONCLUSION: Successful implementation of F-18-FDG-PET as additional imaging method in patients with FUO seems reasonable. This has to be verified by further prospective studies.

[Magnetic resonance tomography in the diagnosis of mandibular osteomyelitis]. / Magnetresonanztomographie zur Diagnostik von Unterkieferosteomyelitiden.

PURPOSE: A prospective study of the value of MRI in the diagnosis of osteomyelitis of the mandible with special reference to the suitability of different MR sequences. MATERIAL AND METHODS: In 13 patients, average age 55 years (12-82), with clinical suspicion of osteomyelitis of the mandible, 18 MRI examinations were carried out (STIR, TSE T2, proton and SE T1 weighted scans with and without contrast, slice thickness 3.5 to 6 mm). Image quality of the sequences was evaluated as well as the suitability of the various sequences for showing the lesion, its location and extent. Activity of the osteomyelitis was judged by the degree of contrast uptake and was correlated with 3-phase bone scintigraphy and with histological findings. RESULTS: In 9 of the 14 cases the findings on MRI and of the scintigraphy agreed with the histology. In two patients the activity of the inflammatory process was exaggerated by the MRI. In another follow-up examination it was slightly underestimated. All lesions were shown to be highly active by the histology were recognized as such by MRI. For the localisation and recognition of the extent of the inflammatory processes STIR sequences and T1 weighted non-enhanced SE sequences proved the most suitable. Contrast medium is essential to evaluate the inflammatory activity. CONCLUSION: MRI is a sensitive diagnostic method; it is as good as 3-phase bone scintigraphy in demonstrating osteomyelitis of the mandible and of its activity but is superior for showing the pathological anatomy.