Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer.

BACKGROUND: The one-step nucleic acid amplification (OSNA) assay is a rapid procedure for the detection of lymph node (LN) metastases using molecular biological techniques. The aim of this study was to assess the reliability of the whole sentinel lymph node (SLN) analysis by the OSNA assay as a predictor of non-SLN metastases. METHODS: Consecutive 742 patients with breast cancer were enroled in the study. The association of non-SLN or ≥4 LN metastases with clinicopathological variables was investigated using multivariate logistic analysis. RESULTS: In total, 130 patients with a positive SLN who underwent complete axillary LN dissection were investigated. The frequency of non-SLN metastases in patients who were OSNA+ and ++ was 19.3% and 53.4%, respectively, and that in patients with ≥4 LN metastases who were OSNA+ and ++ was 7.0% and 27.4%, respectively. The cytokeratin 19 (CK19) mRNA copy number (≥5.0 × 10(3); OSNA++) in the SLN was the most significant predictors of non-SLN metastases (P=0.003). The CK19 mRNA copy number (≥1.0 × 10(5)) in the SLN was the only independent predictor of ≥4 LN metastases (P=0.014). CONCLUSION: Whole SLN analysis using the OSNA assay could become a valuable method for predicting non-SLN and ≥4 LN metastases.

Bone and Tl-201 scintigraphy in a case of hereditary multiple exostoses.

A 17-year-old girl with hereditary multiple exostoses, who was thought to have malignant transformation of an exostotic lesion, was examined by bone and Tl-201 chloride scintigraphy. Scintigraphy showed markedly intense uptake by the lesion, whereas Tl-201 imaging did not. Bone scintigraphy revealed intense to moderate uptake in other exostotic lesions, but none was apparent on the Tl-201 study. The lesion was resected and the histopathologic diagnosis was osteochondroma. Negative findings of Tl-201 scintigraphy may not exclude the possibility of chondrosarcoma, and the utility of this method may be limited. However, Tl-201 scintigraphy appears to have a useful role in differentiating malignant transformation from benign osteochondroma in hereditary multiple exostoses.

[A study on the isolation period of patients with metastatic thyroid cancer treated by 131I according to a new guideline].

In Japan, a new guideline for the release of patients administered 131I was issued by the Ministry of Welfare on June, 1998: The dose rate is under 30 microSv/h at 1 m or the activity in the body is under 500 MBq. This study was designed to set the appropriate isolation period enough to satisfy these limits. A total of 28 patients with the history of total thyroidectomy and metastasis were selected for this study. In these patients, 28 patients were treated with oral administration of 3.7 GBq of Na131I (72 times), and one of 28 patients was once treated with 5.55 GBq of Na131I. Two of them were also received a total of 4 courses of a split dose therapy of 3.7 GBq of Na131I (740 MBq once a week for 5 consecutive weeks = one course). Measurements of the external exposure dose (microSv/h) at 1 m and the urinary excretory radioactivity (MBq) were performed at various times. There was a good correlation of the external exposure dose between standing (x microSv/h) and sitting (y microSv/h) postures (y = 0.99x + 0.406, r = 0.99, p < 0.0001, n = 169). The difference in the external exposure dose before and after urination (x microSv/h) had a significant correlation with the urinary excretory radioactivity (y MBq); y = 16.6x + 24.8, r = 0.96, p < 0.001, n = 41. Also, there was a significant correlation between the predicted value of residual radioactivity in the body (y' MBq) and the external exposure dose (x' microSv/h); y' = 20.8x' + 31.5, r = 0.98, p < 0.001, n = 77. In the patients treated with 3.7 GBq of Na131I, the mean and S.D. values of the external exposure dose (microSv/h) changed as follow: After 6 hr, 168 +/- 40; 24 hr, 52 +/- 23; 48 hr, 20 +/- 15; 72 hr, 10 +/- 9; and 96 hr, 8 +/- 9. The percentages of the patients satisfied the new guideline were as follow; 21.7% at 24 hr, 81.2% at 48 hr and 100% after 72 hr. Therefore the 3-day isolation is sufficient for the patients administered 3.7 GBq of Na131I.

Decreased perfusion of the bilateral thalami in patients with chronic pain detected by Tc-99m-ECD SPECT with statistical parametric mapping.

The purpose of this study was to examine whether the Tc-99m-ECD SPECT can detect any difference between the brain perfusion in patients with chronic pain and normal controls by means of the Statistical Parametric Mapping (SPM96). The subjects were twelve patients with chronic pain (CP group) and twelve normal controls (NC group). After informed consent was obtained, 720 MBq of Tc-99m-ECD was intravenously injected as a bolus. The SPECT data were acquired once for 20 mins from 5 mins after i.v. injection of Tc-99m-ECD, with a triple-head rotating gamma camera. The SPECT data were transformed into a standard stereotactic space, and group comparisons between CP and NC groups were performed on a voxel-by-voxel basis. The subset of voxels exceeding a threshold of p < 0.001 in omnibus comparisons and remaining significant after correction for multiple comparison (p < 0.05) was displayed as a volume image rendered in three orthogonal projections. There was a significant decrease in perfusion in the bilateral thalami in the CP group, suggesting that perfusion in the thalamus generally decreases in patients with chronic pain. Tc-99m-ECD SPECT with SPM96 may be useful for studies of the mechanisms of chronic pain.

Adrenal incidentalomas showing unilateral concordant visualization by adrenocortical scintigraphy: comparison with adenomas in Cushing's syndrome.

An adrenocortical adenoma causing Cushing's syndrome (Cushing's adenoma) produces a unilateral concordant visualization (UCV) imaging pattern in which the adenoma is only visualized on radioiodocholesterol adrenocortical scintigraphy. But because this imaging pattern is also noted in some patients with adrenal incidentalomas, we examined whether the UCV-incidentaloma was essentially identical with Cushing's adenoma and would develop Cushing's syndrome. The subjects were 9 patients with UCV-incidentalomas (mean size, 30 mm; range, 20-45 mm) and 6 patients with Cushing's adenomas (mean size, 28 mm; range, 25-35 mm). Endocrinological evaluations showed several abnormalities including blunted diurnal rhythm of plasma cortisol within the normal range, low plasma ACTH and/or high 24-hr urinary 17-OHCS levels in 8 of 9 patients with UCV-incidentalomas, but these abnormalities did not meet the diagnostic criteria of Cushing's syndrome. Adrenal uptake of the tracer in the patients with UCV-incidentalomas was not statistically different from that in the patients with Cushing's adenomas and had no relationship with hormonal values in either patient group. Tumor size on CT correlated with the levels of 24-hr urinary 17-OHCS (r = 0.75, p = 0.02) and plasma cortisol at 7:00 (r = 0.82, p = 0.007) in the patients with UCV-incidentalomas, but not in the patients with Cushing's adenomas. Although 3 UCV-incidentalomas increased slightly in size, none of 9 patients with UCV-incidentalomas has developed Cushing's syndrome for 4 to 52 months. These results suggest that the UCV-incidentaloma may be essentially different from the Cushing's adenoma and unlikely to develop Cushing's syndrome.

Non-surgical therapy of primary aldosteronism: transcatheter arterial infusion of ethanol into an aldosteronoma.

Primary aldosteronism due to an adrenocortical adenoma can be cured by ablation of the adenoma, which produces an excess of aldosterone (aldosteronoma). This has traditionally been performed by surgical removal of the adenoma. However, some patients with aldosteronomas refuse surgical removal. Therefore, we developed a therapeutic method to ablate an aldosteronoma by transcatheter arterial infusion of ethanol. This method ablated the aldosteronoma in 27 (82%) of 33 treated cases and produced no serious complications, and may be one of the therapeutic choices for aldosteronomas.

[Nuclear medicine for general radiologists: endocrinological examinations].

We reviewed nuclear endocrinological examinations of the thyroid, parathyroid, and adrenal glands that are clinically performed in Japan as well as somatostatin receptor imaging, which is widely used in Europe, the United States, and other countries. 123I thyroid scintigraphy is especially useful in detecting ectopic goiters and differentiating between Basedow's disease and subacute thyroiditis or Plummer's disease, all of which exhibit thyrotoxicosis. 201Tl is useful to detect foci metastasized from well differentiated thyroid cancer and to differentiate malignant from benign tumors. 67Ga-citrate is an agent used for patients suspected of having malignant lymphoma or undifferentiated carcinoma of the thyroid. Radioiodinated MIBG is a specific agent for medullary thyroid carcinoma. 99mTc-MIBI is a good agent for locating hyperfunctioning parathyroid tissues. 131I-adosterol is useful to locate the lesions of primary aldosteronism, Cushing's syndrome, adrenogenital syndrome, and select adenomas among incidental tumors. Radioiodinated MIBG scintigraphy has high diagnostic accuracy in locating pheochromocytomas and neuroblastomas. 111In-labeled octreotide is useful in locating, hormone-producing gastrointestinal and pancreatic tumors including carcinoids, gastrinomas, and insulinomas. Radiolabeled somatostatin receptor analogs are used not only to locate but also to treat malignant somatostatin receptor-positive tumors. We hope that Octreoscan will be available in Japan in the near future.

Transcatheter adrenal arterial embolization of cortisol-producing tumors. Two cases of Cushing's syndrome.

Transcatheter arterial embolization (TAE) was performed in 2 patients with Cushing's syndrome caused by adrenal adenoma by using a mixture of absolute ethanol and iohexol. In 1 patient successful suppression of the hypersecretion of cortisol has continued for 9 months after TAE without complications. However, in the other patient, TAE was discontinued due to marked hypertension and tachycardia induced by a massive release of catecholamines from the embolized "normal" part of the tumor-bearing adrenal gland during the procedure. These results suggest that it is important to perform TAE of only the arterial branches feeding the tumor.

Iodine-123 iodobenzofuran (I-123 IBF) SPECT in patients with parkinsonism.

I-123 IBF is a dopaminergic antagonist which is suitable for SPECT imaging of D2 receptors. The purpose of this study is to evaluate the potential usefulness of semi-quantitative parameters obtained from brain SPECT data of I-123 IBF for differential diagnosis in patients with parkinsonism (PN). Subjects were 10 patients with PN: 2 patients with striato-nigral degeneration (SND), 5 patients with Parkinson's disease (PD), 2 patients with progressive supranuclear palsy (PSP) and one patient with olivo-ponto-cerebellar atrophy (OPCA). The data were acquired with a triple-head gamma camera at 2 hours after intravenous injection of 167 MBq of I-123 IBF. Transverse images were reconstructed by means of filtered backprojection, and attenuation correction was performed by Chang's method (mu = 0.08). The basal ganglia-to-frontal cortex ratio (GFR) and the basal ganglia-to-occipital cortex ratio(GOR) on slices of 5 different thicknesses were calculated. The GFR and GOR were lower in the SND group than in the other disease groups in all slices with different thicknesses (7.2 mm, 14.4 mm, 21.6 mm, 28.8 mm and 43.2 mm). The semiquantitative parameters (GFR and GOR) obtained from brain SPECT data at 2 hours after intravenous injection of I-123 IBF may be useful for differential diagnosis in patients with PN.

Metastatic pulmonary pheochromocytomas: positive I-123 MIBG SPECT with negative I-131 MIBG and equivocal I-123 MIBG planar imaging.

Pulmonary metastases from malignant pheochromocytoma were seen with I-123 MIBG SPECT in a 16-year-old girl but were not visualized with I-123 MIBG planar imaging. She had a left adrenalectomy for a pheochromocytoma 7 years earlier. Two small pulmonary nodules were seen on chest X-ray and CT scans.

Scintigraphic assessment of therapeutic success in aldosteronomas treated by transcatheter arterial embolization using absolute ethanol.

UNLABELLED: Adrenocortical scintigraphy was examined as an indicator of therapeutic success in aldosteronomas treated by transcatheter arterial embolization (TAE) with absolute ethanol (AE). METHODS: Adrenocortical scintigraphy was performed 7 days after intravenous injection of 37 MBq 131I-6-beta-iodomethyl-19-norcholesterol before and after TAE. Complete or incomplete therapeutic success was determined by periodic measurements of the levels of plasma aldosterone and correlated with the scintigraphic results. RESULTS: The aldosteronoma was visualized as a hot nodule in nine patients and a warm nodule in one patient before TAE. Scintigraphy showed a hot, residual hot or warm nodule on seven occasions (six occasions after the first TAE and one occasion after the second TAE) when the techniques were incompletely successful and disappearance on seven occasions when success was achieved (three occasions after the first TAE and one occasion after the second TAE). Of the seven occasions when TAE was unsuccessful, four patients received the second or third TAE to result in complete destruction of the aldosteronoma; three patients underwent unilateral adrenalectomy. CONCLUSION: Adrenocortical scintigraphy can correctly predict the effect of TAE on aldosteronomas and is a valuable indicator for decisions on the necessity of repeated TAE or adrenalectomy.

Numerous sites of increased uptake shown on bone scintigraphy in a case of adult T-cell leukemia.

Bone scintigraphy was performed in a 69-year-old male patient with adult T-cell leukemia suffering from right lower limb pain. Numerous sites of increased uptake were seen in the skull, left clavicle, bilateral humeri, bilateral radii and right femur and tibia. Bone radiographs showed multiple osteolytic lesions, most of which corresponded to the abnormal deposits on the bone scans with 740 MBq of 99mTc-hydroxymethylene diphosphonate. This pattern is rarely reported, but bone involvement of adult T-cell leukemia is not uncommon. Bone involvement was remarkable on the appendicular skeleton when compared with common metastatic bone tumors. Bone scintigraphy may be useful in detecting bone involvement in adult T-cell leukemia.

I-123 iomazenil SPECT in patients with mental disorders.

The purpose of this study is visual evaluation of the distribution of I-123 iomazenil in the brains of patients with various types of mental disorder and to examine whether chronic administration of a clinical dose of benzodiazepine (BZ) affects the binding of I-123 iomazenil to BZ receptors (BZR). The subjects were 10 patients with mental disorders (3 males and 7 females) with a mean age of 26.8 yrs (range 19-39 yrs). Four of 10 patients were administered BZ for over 3 months and the other six were free of BZ for over one month. The SPECT images were obtained at 5-25 min (early) and 170-190 min (delayed), after the bolus i.v. injection of 167 MBq of I-123 iomazenil, with a triple-head gamma camera. The images were visually evaluated and the washout ratios of each region were calculated. In visual analysis, abnormalities were recognized in 5 patients on the delaye SPECT. The abnormalities were recognized more frequently in the superior frontal lobe. The washout ratio was higher in the BZ (+) patient group than in the BZ (-) patient group. I-123 iomazenil is useful, because the SPECT image with I-123 iomazenil reflects the distribution of BZR on the brain and provides the different information from that obtained with perfusion SPECT, X-ray CT or MRI. The rapid washout of I-123 iomazenil from the brains of BZ (+) patients suggests that chronic administration of a clinical dose of BZ affects the binding of I-123 iomazenil to BZR.

[Can 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) evaluate the renal function without blood sampling?: consensus report from multicenter study].

A multicenter study was undertaken in Japan to evaluate the correlation between the percentage of renal uptake of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) estimated by the count-based gamma camera method and the blood clearance of 99mTc-MAG3. Twenty four centers were enrolled and 172 cases were finally analyzed in this study. The renal clearance of 99mTc-MAG3 (TER) was obtained by using a single blood sample taken at 44 min after injection. Comparison of TER and renal uptake provided a coefficient of correlation of 0.874; suggesting that sufficiently accurate quantification of renal function could be obtained from the renal uptake estimate by the gamma camera method. This study also showed that the comparison of renal function might be feasible among patients under the same protocols, although precise and careful consideration is required in each center.

Transcatheter arterial renal and adrenal embolization with iohexol-ethanol solutions. Animal experimental study and clinical application.

RATIONALE AND OBJECTIVES: The authors compared the embolic effect of radiolucent absolute ethanol (AE) with that of a radiopaque iohexol-ethanol (IES) solution for renal ablation in dogs and for the destruction of human aldosteronomas by the technique of transcatheter arterial embolization (TAE) to test whether IES can be an alternative to AE. METHODS: The embolic agents were infused through a balloon catheter into the renal arteries of 17 dogs (9 infused with 0.3 mL/kg AE; 8 infused with IES). The immediate and parenchyma were compared between the two groups. Transcatheter arterial embolization with IES also was performed in three humans with unilateral aldosteronoma. RESULTS: The IES was visualized faintly under fluoroscopy in all dogs. There were no significant differences in embolic effects between the AE and IES. Three patients with aldosteronoma were treated successfully by TAE with IES. CONCLUSIONS: The IES can be used as a "visible ethanol" to improve the safety and ease of ethanol embolization.

[A case of metastatic gastrinomas in the liver visualized by 111In-DTPA-D-Phe-octreotide (111In-pentetreotide)].

A 51-year-old woman with metastatic gastrinomas in the liver was intravenously injected with 80.3 MBq of 111In-DTPA-D-Phe-octreotide (111In-pentetreotide). Planar images were obtained at 4 hr, 24 hr and 48 hr after the injection. SPECT was also performed at 24 hr after the injection. Two metastatic lesions in the liver were visualized on each imaging occasion. 111In-pentetreotide imaging is useful to visualize gastrinomas.

Primary hepatic neuroendocrine carcinoma with multiple metastases: a case report.

We report a rare case of primary hepatic neuroendocrine cell carcinoma with multiple metastases to the liver, lung, diaphragm, bone, and pancreas. The patient was a 45-year-old man with jaundice and a large hepatic tumor measuring 12 x 16 cm at autopsy. Located in the right lobe, it was hyperechoic and inhomogeneous on US, a diffusely low density mass that contained capsule- and septum-like structures enhanced by contrast medium on CT, an inhomogeneously low intensity mass with much lower intensity foci on T1-weighted MRI, and a diffusely high intensity mass containing small higher and lower intensity foci on T2-weighted MRI. These findings are similar to those of a few previously reported cases, but are not specific to this tumor.

Evaluation of a double-injection method for sequential measurement of cerebral blood flow with iodine-123-iodoamphetamine.

UNLABELLED: To test the feasibility of applying N-isopropyl-[123I]p-iodoamphetamine (IMP) for sequential measurements of regional cerebral blood flow (rCBF) with injection of two separate doses in a single procedure, kinetic analysis based on a two-compartment model was done using dynamic SPECT data. A microsphere model analysis without consideration of IMP washout from the brain was also tested for clinical application. METHODS: A dynamic SPECT scan consisting of fifty 1-min scans was obtained on 15 patients using a three-head rotating gamma camera with two separate doses of IMP (111 MBq each) at the beginning and 25 min after scan initiation. The reproducibility of two resting rCBF scans was tested in six patients and the cerebrovascular response shown by increased rCBF with acetazolamide (1 g) was assessed in nine patients. RESULTS: Two-compartment model analysis showed excellent reproducibility of resting rCBF scans and significantly different cerebrovascular reactivity to acetazolamide between areas with and without ischemia. Microsphere model analysis showed smaller values in the first rCBF image by 3% and in the second by 10%, resulting in lower values for cerebrovascular reactivity. The difference in cerebrovascular reactivity between ischemic and nonischemic areas, however, is highly significant. CONCLUSION: The double-injection method for IMP is feasible for two sequential rCBF measurements in a single procedure and is applicable for acetazolamide challenge. Simple microsphere model analysis, as well as a two-compartment model analysis, provide reliable assessment for cerebrovascular reactivity despite the complex dynamics of IMP and are feasible for clinical application.

Age and gender differences in normal myocardial adrenergic neuronal function evaluated by iodine-123-MIBG imaging.

UNLABELLED: Myocardial sympathetic nervous function has been evaluated with 123I-metaiodobenzylguanidine (MIBG) imaging in various cardiac diseases. Heterogeneous distribution of this tracer has been reported. This study was undertaken to assess whether such heterogeneity is related to age and gender. METHODS: Twenty-nine subjects (18 men, 11 women; age range, 21 to 79 yr; mean age 42 +/- 17 yr) with no cardiac disorders were studied. Early (15 min) and late (3-4 hr) planar images were taken, and SPECT images were also obtained 3-4 hr after MIBG injection (111 MBq). The mean counts of the whole heart, mediastinum and the anterior and inferior regions of the heart were obtained to calculate heart-to-mediastinum count ratios, myocardial washout rates and the inferior-to-anterior wall count ratio. On a bull's-eye map of the SPECT images, the left ventricular myocardium was divided into nine sectors to calculate the inferior-to-anterior wall count ratio. RESULTS: There were no significant differences in the heart-to-mediastinum count ratio based on age or gender, but there was a significant inverse correlation between the inferior-to-anterior wall count ratio and age (r = -0.51 on late planar images and r = -0.69 on SPECT; p < 0.01 and p < 0.001, respectively). This correlation was valid in men (r = -0.74 and -0.83, respectively; both p < 0.001), but not in women (r = -0.25 and -0.34, respectively; p = ns). CONCLUSION: Inferior wall uptake of MIBG decreased with age in individuals without cardiac diseases, especially men. Such age- and gender-related heterogeneity should be considered in the interpretation of MIBG images.