Low- versus high-dose radiotherapy for Graves' ophthalmopathy: a randomized, single blind trial.

Orbital radiotherapy (Rx) is a commonly used treatment for Graves' ophthalmopathy (GO), but controlled clinical trials evaluating different Rx doses and application forms have not been performed. In euthyroid patients with moderately severe GO, we randomly compared the efficacy and tolerability of three Rx protocols. Orbital Rx (telecobalt) was administered either in 20 divided fractions of 1 Gray (Gy) weekly over 20 weeks (group A) or in 10 fractions of 1 Gy (B) and 2 Gy (C) daily over 2 weeks. Before and 24 weeks after starting Rx, ophthalmic investigation and magnetic resonance imaging were performed. Response to therapy, defined as a significant amelioration of three objective parameters, was noted in 12 A (67%), 13 B (59%), and 12 C (55%) subjects (C vs. A, P = 0.007). Ophthalmic symptoms and signs regressed most in group A; changes in lid fissure width were -1.5, -0.5, and 0 mm in the A, B, and C groups, respectively (A vs. C, P = 0.005), whereas changes in intraocular pressure (upgaze) were -3, +1, and -1.5 mm Hg, respectively (A vs. B, P = 0.002). The median decreases in proptosis were -2 mm (A, P = 0.0001), -1.5 mm (B, P = 0.02), and -1 mm (C, P = 0.007; A vs. C, P = 0.0380. Visual acuity (+0.15; P = 0.02) and eye muscle motility (bulbar elevation, 30 degrees vs. 37 degrees, P = 0.03, A vs. C, P = 0.0020; abduction, 45 vs. 49 degrees, P = 0.02; A vs. C, P = 0.017) improved in group A only. A significant change in all rectus muscle areas was noted in 14 A (78%), 12 B (55%), and 9 C (41%) subjects (C vs. A, P = 0.002). A decrease in the NOSPECS classes was observed in 12 A (67%), 13 B (59%), and 13 C (59%) patients (A vs. B/C, P = 0.01). Rx-induced conjunctivitis was not observed in group A, but was seen in 4 B (18%) and 8 C (36%) subjects (C vs. A, P = 0.003). At 24 weeks, satisfaction rates were 67%, 59%, and 55% in the A, B, and C groups, respectively (C vs. A, P = 0.008). Thus, in patients with moderately severe GO, similar response rates were observed for low and high Rx doses, but the 1 Gy/week protocol was more effective and better tolerated than the short arm regimens.

Changes of circulating thyroxine, triiodothyronine and reverse triiodothyronine after radiographic contrast agents.

Thyroid function was studied for 42 days in 58 patients, 28 of whome had euthyroid goiter, after urography (diatrizoic acid), cholangiography (ioglycamic acid), and cholecystography (Naiopanoate). After urography and cholangiography short-lived increases of the serum thyroxine occurred in a few patients, but the mean thyroxine and triiodothyronine concentration did not change. By contrast, 7 days after oral cholecystography serum thyroxine had risen consistently by 22% with a concomittant rise of the free thyroxine, while triiodothyronine declined by 15%. The thyroxine metabolite 3,3',5'-triiodo-1-thyronine (reverse T3) rose by 50% and serum thyrotropin concentration doubled. After 42 days thryoxine and triiodothyronine had returned to baseline, and none of the 58 patients developed clinical hyperthyroidism. In patients with severe myxoedema kept on a constant replacement dose with 1-thyroxine NA-iopanoate produced similar changes with the exception of the rise of the serum thyroxine. The primary event after Na-iopanoate seems to be a fall of the serum triiodothyronine, which in turn augments thyrotropin and indirectly thyroxine secretion. the marked and sometimes sustained rose of serum thyroxine after cholecystography may lead to the erroneous diagnosis of hyperthyroidism.

Somatostatin receptor scintigraphy in central nervous system tumors: role of blood-brain barrier permeability.

UNLABELLED: Somatostatin receptors are expressed in meningiomas and low-grade gliomas, raising the hope that scintigraphy with 111In-DTPA-D-Phe1-octreotide might be helpful in the in vivo localization, differential diagnosis and postoperative/postradiotherapy brain tumor follow-up. METHODS: Indium-111-DTPA-D-Phe1-octreotide scintigraphy and brain scintigraphy using 99mTc-DTPA as a nonspecific tracer for blood-brain barrier integrity were simultaneously performed in 60 patients with CNS tumors using dual-isotope acquisition mode SPECT. For 23 patients, the scintigraphic findings were also compared with in vitro somatostatin receptor autoradiography of surgical biopsy specimens. RESULTS: In meningiomas (located outside the blood-brain barrier), the somatostatin receptor scan showed all tumors and scintigraphic signal intensity correlating with in vitro SSR density positive in all meningiomas. Less contrast was seen on 99mTc-DTPA scans. In all tumors inside the blood-brain barrier, the 111In-DTPA-D-Phe1-octreotide scan visualized the tumors with a disrupted blood-brain barrier, as seen by 99mTc-DTPA scintigraphy. Discrepancies, however, were observed between somatostatin receptor scintigraphy and in vitro receptor autoradiography. CONCLUSION: Combined somatostatin receptor and 99mTc-DTPA scintigraphy may be helpful for noninvasive differentiation between meningiomas and other CNS tumors. False-negative scans were observed as a result of shielding by the intact blood-brain barrier. Interpretation of negative and positive somatostatin receptor scans in CNS tumors must therefore be done with caution.

Renal pathology after arterial yttrium-90 microsphere administration in pigs. A model for superselective radioembolization therapy.

RATIONALE AND OBJECTIVES: To test the selectivity of tissue damage in radioembolization, the authors performed an experimental study using superselective administration of yttrium-90 particles to deliver up to 100 Gy to the porcine kidney. Patterns and severity of damage in test organs were compared with controls, and the feasibility of this model is discussed. METHODS: Eight sows were included in the study. Bio-Rex 70 particles were applied via selective catheterization of the renal artery. Four pigs received inactive particles and four pigs received active particles. Organ distribution and shunting of yttrium-90 were determined, and kidney damage patterns were histologically analyzed. RESULTS AND CONCLUSIONS: The model demonstrates that yttrium-90-labeled resin particles can superselectively be applied. Retention of beta activity in the target organ was more than 95%. In addition to tissue shrinkage from mechanical obstruction, considerable damage ensued mainly by radiation-induced arterial necrosis and arteritis.

MRI-assisted radiation therapy planning of brain tumors--clinical experiences in 17 patients.

A new and simple method for precise determination of lateral opposed treatment portals was developed and used in 17 patients. Compared to CT, MRI led to significant changes of portals in 59% (10/17) of cases. Individual shielding blocks could be precisely designed by use of our new method. MRI is the procedure of choice in local radiation therapy planning of brain tumors.

[Role of renal function and calcemia in demonstration of kidneys in 99mTc-diphosphonate skeletal scintigrams (author's transl)]. / Nierendarstellung im 99mTc-Diphosphonat-Skelettszinitigramm in Abhängigkeit von Nierenfunktion und Kalzämie

Normally, in 99mTc-diphosphonate-skeletal scintigrams the kidneys are delineated with the same intensity as the lumbar spine; This is not the case in patients with reduced renal function. In a series of 20 patients with varying degrees of renal insufficiency, a continuous decrease in the renal intensity with increasing serum creatinine was seen: clearly recognizable decreased renal intensity in patients with serum creatinine over 2 mg%, and no visualization of the kidneys in patients with serum creatinine over 8 mg%. This effect is intensified through a simultaneously existing hypercalcemia has the opposite effect, i.e., the intensity decrease is partially prevented. In patients with normal renal function a hypercalcemia even leads to an increased renal intensity. As a further cause for excessive renal intensity, an increased parenchymal transit time was found in the radionephrography in 5 out of 11 patients with normal serum creatinine in whom the increased renal intensity in the skeletal scintigram was a chance finding.

[The reliability of scintigraphic criteria of the lungs concerning the estimation of mediastinal involvement in case of bronchial carcinoma (prospective study) (author's transl)]. / Die Zuverlässigkeit lungenszintigraphischer Kriterien für die Beurteilung des Mediastinalbefalls beim Bronchialkarzinom (prospektive Studie)

The goal of this prospective study is to determine the reliability of the scintigraphic diagnosis of mediastinal involvement in patients with bronchial carcinoma, as well as to establish the value of each individual scintigraphic criterion. Ninety-four patients, all of whom were hospitalized because of suspicion of bronchial carcinoma were examined using 133-Xenon i.v., 133-Xenon gas inhalation, and 99m-Tc-MAA i.v. (macroaggregated albumin or microspheres of human albumin). The suspicion was confirmed in 77 patients. -The most reliable scintigraphic criteria are: 1. a localized delayed appearance of the activity in the afflicted lung area during the first 20 sec of the 133-Xenon i.v. series, and 2. the presence of a "dead-space" ventilation. Activity remaining in the area of the subclavian vein or the superior vena cava up to 10 min after the injection of 133-Xenon i.v. must be very carefully interpreted. Sixty-five patients underwent both mediastinoscopy and scintigraphy: in 44 patients (= 68%) the findings in both examinations were the same. Compared to the final diagnosis (mediastinoscopy, operation) there were 20 (= 30%) false negative but only one (= 2%) false positive scintigraphic diagnoses made. -When the scintigraphic criteria of hilar or mediastinal involvement are fulfilled, then the patient is practically certain to be no longer radically operable. This assertion is valid even when the mediastinoscopy is normal.

[Sonography of bone metastases--its place in comparison with computed tomography and conventional x-ray diagnosis]. / Sonographie bei Skelettmetastasen--Stellenwert im Vergleich zur Computertomographie und konventionellen Röntgendiagnostik.

The value of CT, conventional radiography and ultrasound was compared in 40 patients with 52 skeletal metastases. For superficial lesions, the combination of sonography and conventional radiography was equivalent to CT in showing the extent of bone destruction and soft tissue involvement. As expected sonography was unsatisfactory for deeper lesions. Sonography can provide useful information for planning radiation therapy for superficial lesions, but it does not replace conventional radiography.

[Methods for the superselective radioembolization of liver tumors with 90yttrium-resin particles]. / Methodik der superselektiven Radioembolisation von Lebertumoren mit 90Yttrium-Resin-Partikeln.

An improved technique for radioembolization of non-resectable liver tumours is described. 90yttrium-labelled Bio-Rex-70 particles which show high stability and good tissue tolerance are applied superselectively via the tumour-feeding artery using a microcatheter. The procedure includes both diagnostic and therapeutic angiography. Angiography is complemented by angioscintigraphy (99mTc-MAP) and an i.v. 99mTc-colloid scan of the liver. Thus it is possible pretherapeutically to evaluate tumour volume and dose distribution both in and outside of the liver, and in the lung due to shunt. These estimates were re-evaluated posttherapeutically. Radioembolization can thus be quantified and the doses absorbed by the tumour as well as the liver and lung can be calculated.

[Estimation of lung water with 131I-antipyrine and 99mTc-HSA (author's transl)]. / Extravaskuläre Lungenwasserbestimmung mit 131J-Antipyrin und 99mTc-Humanserumalbumin.

Extravascular lung water is estimated in vivo from indicator dilution curves of diffusible and non-diffusible tracers utilizing their different transit times as they pass the lung microvessels. 131I-antipyrine as the diffusible and 99mTc-HSA as the non-diffusible tracer were injected simultaneously, using a pneumatic injector. Indices for rELW/V and rELW/F were calculated using programs previously published, and gave numerical values for the presence and intensity of pulmonary interstitial oedema. Inaccuracies due to sequential inputs are avoided. 131I-antipyrine has a more convenient pulmonary interstitial oedema. Inaccuracies due to sequential inputs are avoided. 131I-antipyrine has a more convenient shelflife and can therefore serve for emergency and follow-up examinations. The results do not differ significantly form those with 123I-antipyrine, and the higher radiation burden is tolerable. A mobile set-up for bed-side measurements is described.

Separation of autonomous function from cell density in non-immunogenic hyperthyroidism--II. quantified comparison before and after radioiodine therapy.

Regional autonomous cell mass (Q: cell density ratio) and function (T: toxicity index) were compared by double isotope parametric thyroid scintigraphy (Als et al., Nucl. Med. 1995; 34) in 53 patients with non-immunogenic hyperthyroidism before and after radioiodine therapy (aRIT) and showed a break-down (medians) of Q: 4.3-->1.0 (toxic adenomas: TA), 2-->1.1 (multifocal functional autonomies: MFA)(p < 0.0001) as of T: 96-->1.7 (TA), 15-->1.1 (MFA) (p < 0.001). Five functional aRIT patterns resulted: euthyroidism (n = 37, 70%), at half with scarred/non-scarred autonomous areas (low/higher T, respectively), primary hypothyroidism (n = 4), residual hyperthyroidism (n = 7), secondary hyperthyroidism (n = 5). The last two groups with persistent subnormal TSH values were clearly separated by divergent T, thyroxine and triiodothyronine levels. A resulting T > 1 may represent a clinically sub-critical mass of residual autonomous tissue. This new technique facilitates individual pretherapeutic evaluations and aRIT quality control.

[Trend scintigraphy]. / Trendszintigraphie.

Focal changes in activity concentration for given time function. The increase per time interval is calculated for each pixel and arranged into a result matrix. Areas with increasing activity are displayed in a "positive trend scintigramm", those with decreasing activity in a "negative trend scintigram", using a gray scale of color format. Statistical fluctuations are suppressed using this method; the data smoothing over the chosen time period and the fact that several individual pictures are included in the calculations provide displays with increased informational content as compared to serial imaging methods. The clinical interpretation of localized changes in activity concentration during a specific time interval is facilitated. The method is simple, can be adapted to different camera and computer systems, and requires no additional examination procedures on the patient.

Optimal sampling times for OIH-clearance calculations using a two-compartment/two-sample method.

Orthoiodohippurate (OIH) clearance data obtained with the two-compartment/two-sample method of Lear which uses varying sampling time combinations, were compared with those of the reference two-compartment/multi-sample method of Sapirstein. A total of 35 studies were performed in 33 adult patients. The OIH clearance values determined by the reference method ranged from 107 to 883 ml/min/1.73 m2, with a median of 406 ml/min/1.73 m2. It was ascertained that the precision of the Lear method is partially dependent upon the sampling time combination. The most reliable results with the Lear method in this patient population were obtained by taking a first sample at approximately 8 min p.i., and a second sample at 32 min p.i. or later.

[Synoviorthesis of the knee joint with 32P-chromic phosphate (author's transl)]. / Die Synoviorthese des Kniegelenkes mit 32P-Chromphosphat.

32P-CrPO4 in colloid form has been used for radiosynoviorthesis. There were no acute or subacute side reactions observed. The therapy results were equal to those following 90Y colloid application: 60% very good to good results after 6 months. The substance can be kept on stock since it has a relatively long shelf-life. The cost reduction and the simplification of treatment planning have proved to be the most important advantages of 32P-CrPO4.

Immunogenic and non-immunogenic hyperthyroidism. Recent trends in prealpine Switzerland and in coastal Poland.

Annual occurrences of immunogenic (IH) and non-immunogenic hyperthyroidism (NIH) between Berne (1976, 1982, 1991) and Szczecin (1973, 1980, 1991) were compared. Out of 21,025 patients referred for thyroid examinations, 10.1% (average) were hyperthyroid. In Berne (former endemic goiter region) and Szczecin (without goiter endemicity) IH occurred in 41% and 68%, NIH in 59% and 32% of hyperthyroid patients, respectively. Within a stable incidence of NIH in Berne, toxic adenomas (TA) decreased from 41% (1976) to 17% (1991) (p < 0.005). In Szczecin, where iodine deficiency is in an early stage, the TA frequency did not change significantly: from 24% (1973) to 28% (1991). Increases of TA or of multifocal functional autonomy apparently "mark" incipient or, respectively, decreasing deficiencies in nutritious iodine. Hyperthyroid patients in Berne compared to Szczecin were older, both with IH (54 versus 45 y) and NIH (65 versus 52 y). Age at diagnosis was stable in Berne but increasing (p < 0.05) in Szczecin (from 43 to 52 y).

[Hyperthyroidism in thyroid cancer. Retrospective study of 53 cases]. / Hyperthyreose bei maligner Struma. Retrospektive Erhebung mit 53 Fällen.

Hyperthyroidism was diagnosed in 53 of 273 thyroid carcinoma patients at the time of their first examination (between 1971 and 1983). This corresponds to 19.5% of these mainly well-differentiated thyroid cancers. In 24 (45%) patients the hyperthyroidism and the thyroid carcinoma were two separate distinct illnesses: of 4 patients with Graves' disease (1.5% of 273), 2 had been operated because of an additional solitary cold nodule, and in the other 2 an occult carcinoma was found intraoperatively. Twenty patients of this group had Plummer's disease: there was a malignant cold nodule within a multinodular goiter with multifocal functional autonomy (MFA)(n = 14) or a carcinoma located near the solitary hot nodule of the toxic adenoma (TA)(n = 6). In these patients the distribution of the different histologies was about the same as in other thyroid cancer patients from this region. The remaining 29 patients (55%) had Plummer's disease, 28 with the classical finding of a solitary toxic adenoma, in which the hot nodule and the malignant tumor were identical. It was possible to confirm this identity histologically in 10 out of 24 cases, retrospectively. Eight of these patients had metastases with radioiodine uptake at the time of the first examination. Of the tumors in this group, 24 were follicular and 5 papillary carcinomas. As a rough estimate, one malignant, scintigraphically hot tumor is found for every 50 benign toxic adenomas. Criteria for the differentiation are: recent growth of the nodule, tumor size of greater than 5 cm diameter or greater than 35 g and an elevated T3-level of less than 0.06 nmol/l/g tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Separation of autonomous function from cell density in non-immunogenic hyperthyroidism. I. Quantification by double-isotope parametric scintigraphy.

UNLABELLED: A new quantitative subtraction method of thyroid scans is proposed which shows that regional function (F) by far exceeds regional cellularity or cell density (C) in potentially toxic thyroidal areas of non-immunogenic hyperthyroidism (NIH). METHODS: A multistep processing of radioiodine and MIBI thyroid scans of patients with non-immunogenic hyperthyroidism led to normalized images of regional function excess and of perinodular enhancement. Two numeric factors were derived from regions of interest: Q (cell density ratio) comparing MIBI uptake in autonomous and suppressed areas and T (toxicity index): the maximal F/C contrast. RESULTS: Q never exceeded 61; T, however, expanded toxicity levels over a range of 6-8735 with toxic adenomas (median = 165) and with hot areas of multifocal functional autonomy (median = 15). T was weakly correlated to serum TT3 (r = 0.41), but not to autonomous tissue mass, ultrasonographic or cytologic criteria. CONCLUSIONS: T is governed by inherent features of autonomous tissue and the response of the imbedded thyroid tissue to TSH stimulation. This standardized technique consolidates experiences from visual analysis; the huge T range mirrors the natural evolution from compensated autonomy towards hyperthyroid, decompensated stages.

[Scintigraphic use of 87Y during 90Y therapy of bone metastases]. / Szintigraphische Verwendung von 87Y bei der 90Y-Therapie von Knochenmetastasen.

Carrier-free 87Y is produced by cyclotron irradiation of Rb. It decays with a half-life of 80.3 h, transforming via 87mSr to stable 87Sr with the emission of gamma lines of 0.48 and 0.39 MeV. Experience in 6 patients shows good scan quality and correspondence between 99mTc-DPD and 87Y images useful in 90Y-citrate therapy for bone metastases. 87Y offers new possibilities of studying biological kinetics in 90Y therapy. To avoid contamination this should only be used in departments with possibilities of radioactive waste storage and controlled disposal.

[Selective double-isotope coronary scintigraphy with 99mTc- and 111In-HSA-microspheres]. / Zur Technik der selektiven Doppelisotopen-Koronarszintigraphie mit 99mTc-und 111In-HSA-Mikrosphären.

A small fraction of a commercially available kit for the preparation of human serum albumin (HSA)-microspheres is labeled with 111In or 99mTc. The regional coronary blood flow is determined after selective injection of these labeled microspheres at rest and during rapid atrial pacing using a double-isotope coronary scintigraphy with a gamma camera.