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The guidelines for publishing economic evaluations require a statement of the economic importance of the analysis and the viewpoint from which it has been carried out, as well as specification of at least two alternative programmes or interventions, the form of economic evaluation, the outcome measure, the method of costing, the time horizon and adjustment for timing of costs and benefits (e.g. by a discount factor), and the allowance for uncertainties (e.g. by implementation of a sensitivity analysis). The decision analysis can be based on clinical trial data, on retrospective or administrative databases, or on modelling. The choice of outcome measures is the key issue in an economic evaluation. In cost-effectiveness analysis, benefits are usually measured in natural units. This is the form of economic evaluation most frequently used in nuclear medicine. Endpoints of effectiveness applied in studies in this field have been procedures avoided, procedures initiated, cardiac events, survival probability, morbidity, quality of life and protracted or failed surgical procedures. In other instances, surrogate endpoints have been used such as metastases detected, staging, viability or tumour response. This, however, limits comparability of cost-effectiveness considerably, as proof of a change in the health outcome cannot be obtained. Measures of utility such as QALYs (quality-adjusted life years) have so far only been applied for decision tree analysis. Useful examples of economic evaluation studies in nuclear medicine are presented here for fluorodeoxyglucose positron emission tomography (FDG-PET) in the preoperative staging of non-small cell lung cancer, for FDG-PET in differentiating indeterminate solitary pulmonary nodules, for somatostatin receptor scintigraphy in detecting metastases of carcinoid tumours, for routine preoperative scintigraphy with sestamibi in patients with parathyroid adenoma, for periodic measurement of thyroid-stimulating hormone in detecting mild thyroid failure, for diagnostic algorithms including a lung scan in patients with suspected pulmonary embolism, for myocardial perfusion imaging as an incremental prognostic factor in patients with coronary artery disease, and for the use of radioiodine as first-line therapy of Graves' hyperthyroidism and of toxic nodular goitres. Further evaluations of effectiveness or utility should be carried out within a multidisciplinary framework to ensure that nuclear medical procedures are included in the general management guidelines.

The diagnostic and therapeutic impact and the cost-effectiveness of positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) will depend on the role for which the tests are used. In 68 patients with advanced malignant melanoma, original sets of FDG-PET images from various institutes were compared with findings obtained by ultrasonography, conventional radiology, computed tomography (CT) and magnetic resonance imaging. In 22 patients, all examinations were undertaken within 2 weeks and strategies of staging were analysed. In 46 patients, only some of these examinations were performed within this time period, and comparison of methods was restricted to the examined organs. The occurrence of metastasis, without specifying the number of foci, was detected by either conventional staging with CT or by PET in 20 of 22 patients. None of these patients were up- or down-staged by FDG-PET compared with CT staging. In the 68 patients as a whole, FDG-PET detected fewer pulmonary and hepatic metastases and fewer cerebral foci, but more lymph node and bone metastases than conventional radiology or CT. For the detection of lymph node or skeletal metastases, false-positive FDG-PET findings were taken into account when compared with follow-up data. In advanced melanoma, FDG-PET did not influence the pattern of subsequent diagnostic testing. Thus, indications for FDG-PET include pre-metastatic melanoma, localized lymph node metastases and monitoring of the response to treatment.

Aim: As first-line therapy of hyperthyroidism caused by Graves' disease antithyroid drugs are favoured in Europe, while radioiodine therapy is favoured in the USA. Radioiodine therapy has become more economic in Germany since the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines., Method: Sensitivity analyses took into account the long-term relapse rate of conservative or radioiodine therapy, use of diagnostic tests, level of health insurance, drops in productivity and a discount factor. Costing models included the costs of follow-up care over 30 years. The costs of the hospitalisation for radioiodine therapy were calculated for 300 patients, discharged with 250 MBq 1-131 residual activity., Result: Antithyroid drugs were considered cost-effective when they achieved relapse rate of 50% or less, a cut in the number of tests needed and reduced working hours. Failure to meet any one of these conditions makes primary radioiodine therapy more cost-effective in 1593 of 1944 calculated costing models. Repeated conservative therapies will increase clearly the overall costs., Conclusion: Radioiodine is a cost-effective, first-line therapy in patients with a special risk of relapse after primary conservative therapy (goitre, younger patient, persistent elevated TSH-receptor-antibodies or Tc-uptake).

Additional or expensive diagnostic imaging had to prove prospectively their diagnostic efficacy, their therapeutic efficacy, or their patient-outcome efficacy. The adherence to methodologic standards in the cost-effectiveness literature is required. Based on the bone scintigraphy in oncologic patients with a low prevalence of bone metastases, the cost-effectiveness is questionable. The economic role of 99m-Tc MIBI mammoscintigraphy and of the imaging for carcinomas of unknown origin is discussed controversially. Based on the reimbursement of the positron emission tomography (PET) in the USA and in Switzerland, cost-effectiveness literature and decision trees for cost-utility analyses are reviewed. PET imaging was cost-effective in non-small-cell lung cancer, in solitary pulmonary nodules, in recurrent colorectal cancer, in metastatic melanoma and in recurrent head and neck cancer with reduced costs of management. The German health insurance calls for PET-data based on the national reimbursement.

Whether or not thyroid-associated orbitopathy is exacerbated by radioiodine therapy is a matter of controversy. Several risk factors can be listed: pre-existing active ophthalmopathy, hypothyroidism following radioiodine therapy, elevated T3 levels during radioiodine therapy, recurrent or persisting hyperthyroidism after low-dose radioiodine therapy and smoking. Recent studies and own data demonstrate that worsening of pre-existing thyroid-associated orbitopathy after radioiodine therapy can be prevented by the administration of glucocorticoids. Even in patients without evident ophthalmopathy the prophylactic use of glucocorticoids is in our opinion justified to minimize a small but known risk of the development of ocular symptoms. Larger prospective randomized studies are needed to establish the optimal dose and duration of the required anti-inflammatory therapy.

Cost accounting has shown that the volume of tissue to be treated is the decisive factor in determining the cost of radioiodine therapy (RAITh). In the case of large goitres, the costs of excision (5.185 DM) and radioiodine therapy (5.562 DM) are, to a large extent, equivalent. Under the 1993 regulations for radiation protection, RAITh was cost-effective for treatment of toxic multinodular goitres up to volumes of 57 ml. However, new maximum permissible levels of radioactivity on discharge from hospital (250 MBq iodine-131 residual activity) have raised this threshold volume to 90 ml. In Germany, remuneration for a goitre resection is calculated from standard charges for total treatment without any consideration of the size and spectrum of medical services offered by different clinics, while remuneration for RAITh comes from payments for basic and specific, departmental medical services. University clinics with departments of nuclear medicine have relatively high basic costs. In the first quarter of 1998, the length of hospitalisation after RAITh (for all indications combined) was 4.6 days in university hospitals in Germany. Owing to this shorter length of hospitalisation, the payments received in some clinics fell far short of the total costs of this treatment calculated by cost accounting.

Aim: Consequences of the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines (residual activity of 250 MBq for I-131) were calculated for duration of stay and radioiodine therapy cost management., Methods: For 601 consecutively admitted patients with hyperthyreosis, actual duration of stay and duration of stay according to previous guidelines (from 1993) were calculated, as well as duration of stay according to recommended values. Following BPflV statutes, cost-analysis considered the cause and volume of goitre, and by using sensitivity analyses included a range of diagnostics, service assessment, and duration of stay., Results: Duration of stay following I-131 therapy (in Germany) is expected to fall by 35-50% (average future stay 4.0 +/- 2.8 days), average costs from DM 4,452 to DM 3,680 (-17.4%). Not including pretreatment diagnostics, cost reduction (service assessment 17-24%) was estimated at 21-25%. Compared to strumectomy, I-131 therapy costs are expected to be lower for goitres (Graves' disease) up to at least 60 ml, toxic nodules of at least 25 ml, and toxic multinodular goitres of at least 90 ml., Conclusion: In the future, I-131 therapy will be more cost-effective even with larger goitres. Since reimbursement is determined by the duration of stay, new reimbursement procedures are discussed in this paper.

Aim: FDG-PET and MIBI-scintigraphy with SPECT were compared to [131I]-whole-body scintigraphy (WBS) and morphologic imaging in the follow-up of differentiated thyroid cancer. Their influence of therapy-planning was analysed., Methods: In 50 consecutive patients (papillary/ follicular/variants of a follicular carcinoma: 33/13/4; primary status: pT1/2/3/4: 3/16/9/22) FDG-PET of neck/chest and MIBI-whole-body scan including SPECT were performed during hypothyreosis and before WBS. Morphologic imaging was done by MRI in all and by CT of the lung without contrast media in 21 patients., Results: The complete extent of metastases was detected by FDG-PET in 11 and by MIBI-scintigraphy also in 11 of 22 patients with evidence of disease. The combined evaluation of WBS and FDG-PET as well as of WBS and MIBI-scintigraphy held true in 18 of 22 patients. Limiting FDG-PET or MIBI-scintigraphy to patients with elevated thyroglobulin (Tg)-levels and negative WBS only, would not, therefore, alter the sensitivity of this algorithm. The diagnostic benefit of FDG-PET and MIBI-scintigraphy was confined to lymph node metastases. The 1 cm limit for lymph node size in morphologically based imaging did not apply to FDG-PET and MIBI-scintigraphy. None of the 6 patients with small (< 1 cm) pulmonary metastases showed either FDG- or MIBI-uptake, but could be diagnosed by spiral-CT., Conclusion: WBS cannot be replaced by FDG-PET or MIBI-scintigraphy; neither of the latter was better than the other. Rising Tg-levels, negative WBS and the exclusion of pulmonary metastases by spiral-CT define the constellation in which FDG-PET and MIBI-scintigraphy can provide data of therapeutic relevance.

Metastases of differentiated thyroid cancer may show different uptake patterns for fluorine-18 fluorodeoxyglucose and [131I]NaI. FDG positron emission tomography (PET), iodine-131 whole-body scintigraphy (131I WBS) and magnetic resonance imaging were performed in 58 unselected patients, and spiral computed tomography (CT) of the lung in 25 patients. Thirty-eight patients presented with papillary carcinomas, 15 patients with follicular carcinomas and five patients with variants of follicular carcinoma. Primary tumour stage (pT) was pT1 in 3, pT2 in 19, pT3 in 11 and pT4 in 25 cases. For the detection of metastases, FDG PET was found to have a sensitivity of 50%, 131I WBS a sensitivity of 61%, and the two methods combined a sensitivity of 86%. When FDG PET was limited to patients with elevated thyroglobulin (Tg) levels and negative 131I WBS, the sensitivity of this algorithm was 82%. Of the 21 patients with lymph node metastases, seven presented with FDG uptake but no iodine uptake. In four of them, a second FDG hot spot appeared in a lymph node metastasis of normal size. Five of the seven patients underwent surgery. None of the eight patients with pulmonary metastases smaller than 1 cm exhibited FDG uptake, while five of them had iodine uptake. All had positive results on spiral CT. In conclusion, FDG PET cannot be substituted for 131I WBS. If the Tg level is elevated and 131I WBS is negative, FDG PET can be used to detect lymph node metastases and complements anatomical imaging. A spiral CT of the lung is useful to exclude pulmonary metastases before planning a dissection of iodine-negative lymph node metastases.

Unlabelled: A prospective study was performed to compare the sensitivity and accuracy of ultrasound (US), computed tomography (CT), and single photon emission computed tomography (SPECT) as a bone scan to detect subclinical invasion of the mandible by squamous cell carcinoma of the oral cavity and floor of mouth., Methods: The present study reports data on 35 patients with squamous cell carcinoma of the oral cavity. SPECT, mandibular orthopantomography (OPG), US, CT and magnetic resonance imaging (MRI) were performed as well as histologic examination of resected mandibles. Transverse slices of 12 mm thickness were reconstructed for SPECT and semi-quantitative assessment of radionuclide uptake was performed with a scoring system based on comparisons of tracer uptake in the mandible to that in an unaffected part of the mandible. Lesion to non-lesion count ratios in the mandible in 3 h SPECT images were calculated. OPG, US and CT were evaluated for comparison., Results: In 12/35 patients, histologic examination showed carcinoma infiltrating mandibular bone. SPECT correctly predicted mandibular invasion in 11/12 cases, with no false-positive results. CT detected correctly 3/12 lesions, while OPG and ultrasound each demonstrated 2/12 tumors., Conclusion: Bone SPECT was found to provide an accurate means for assessing tumor invasion to the mandible by intraoral squamous cell carcinoma. As a complementary study to one of the other imaging modalities it was shown to have a high specificity, indicating that it should be performed routinely in patients with suspect mandibular bone involvement by causes.

Aim: Cost-analysis of strumaresection and radioiodine treatment in patients with hyperthyreosis., Method: Matched by age, sex, comorbidity, volume of goiter, and entity of hyperthyreosis 18 patients of a clinic of surgery, and 28 patients of a clinic of nuclear medicine were analysed by the reimbursed costs, and by a retrospective calculation of the real costs., Results: Based on the rate for the reimbursed costs the radioiodine treatment (6450 DM) was more favourably than the strumaresection (7562 DM); based on the calculation of the real costs including regional specialities there was a minimal difference in favour of the strumaresection (5185 DM versus 5562 DM) because of the selection of large goiters (median 53 ml), the longer hospitalisation after radioiodine treatment due to legal reasons (12.5 days), and the frequent controls before and after the radioiodine treatment. Most important cost-factor of the radioiodine treatment was the volume of goiter, most important cost-factor of the strumaresection was the age of the patient. The treatment of Graves disease was more expensive than that of autonomy in surgery as well as in nuclear medicine., Conclusion: In order to achieve cost-minimization, radioiodine treatment should be prefered in cases of small goiters or in older patients.

Background: Monoclonal gammopathies-including so-called monoclonal gammopathies of undetermined significance-MGUS-may cause polyneuropathies, even if immunoglobulin concentrations are within a normal range., Case Report: We report on a patient with a rapidly progressive polyneuropathy with severe motor disturbances in whom a small amount of a monoclonal IgM kappa cryoglobulin was found. Only by extensive, repeatedly performed diagnostic procedures could scattered lymphoma cells be detected. Nonspecific immunosuppression had been unsuccessful but eventually a more specific chemotherapy led to an almost complete, sustained recovery., Conclusion: This case shows that in patients with a polyneuropathy of uncertain etiology monoclonal immunoglobulins should be looked for and that a MGUS can precede a lymphoma. Therefore these, patients with a MGUS and clinical deterioration despite conventional immunosuppressive treatment should undergo large-scale diagnostic check-up to make sure that the chance for an adequate chemotherapy is taken.

The current level of knowledge about radioiodine therapy (RITh) for well-differentiated thyroid carcinoma under consideration of the recent literature is summarised. In RITh for thyroid carcinoma two major fields can be distinguished: the ablation of the thyroid remnant and the therapy of recurrences resp. local and distant metastases. New large American studies indicate, that the prophylactic post operative ablation of the thyroid remnant in primary tumours over 1.5 cm in diameter is linked with a distinct improvement of the long-term prognosis. The RITh is effective also in distant metastases, if applied early, when the tumour volume is still small. The prerequisite is an appropriate follow-up. Surveys about the application of RITh for well-differentiated thyroid carcinoma in Europe and in the USA reveal that uniform treatment recommendations designed to conform interdisciplinary demands are urgently required.

175 matched skeletal x-ray examinations were carried out by digital luminescent radiography (DLR) and conventional screen-film system combinations. In digital luminescent radiography (DLR) two differently postprocessed images were obtained from one x-ray exposure: A display with low spatial frequency enhancement was opposed to a second display with high edge enhancement. Conventional and digital images were evaluated randomly and separately by four radiologists using a questionnaire. DLR proved to be diagnostically equivalent to the conventional technique except for a diminished visibility of subtle erosions and fissures. As major advantages of DLR maybe pointed out that faulty exposures were avoided by the automatic adjustment of image brightness and that the soft tissue margins could be more easily delineated in displays with high edge enhancement than in conventional radiography. However, digital displays with high edge enhancement did not provide additional diagnostic information and led to artifacts at the edges of metal prostheses.

Morphological findings recorded from chondromatous tumors of unknown biological behaviour (n = 40) were compared with those obtained from unequivocal chondrosarcomas (n = 27), and the histological results were evaluated by clinical outcome. The morphological details were analysed by histological set up and summarized by Mirra et al. (1985): Two benign patterns, the enchondroma encasement pattern and the island of cartilage patterns, were the most common findings in cartilaginous tumors of unknown biological behaviour. Malignant patterns, such as chondrosarcoma permeation, invasion of the Haversian system, soft tissue mass and bands of fibrosis patterns were detected only in unequivocal chondrosarcomas. However, the enchondroma encasement pattern could be focally demonstrated also in central chondrosarcomas (n = 3), a phenomenon, which in our opinion could not be interpreted as being indicative of a preexisting benign lesion. Morphological classification of chondromatous tumors of unknown biological behaviour, as a group of benign cartilaginous tumors, enables their discrimination from unequivocal chondrosarcomas. This was also confirmed by the significant difference (p = 0.0065; Mantel-Cox) among survival curves after Kaplan and Meier (1958). We conclude that the above criteria, when applied with due caution, are helpful in classifying chondromatous tumors.

In a 22-month-old boy a fibrous metaphyseal defect (FMD) was diagnosed by radiological follow-up examinations. The initial radiological finding could not be differentiated from metaphysitis because of its early manifestation and stage. Eleven months later, magnetic resonance imaging (MRI) with Gadolinium (Gd)-DTPA demonstrated a small central area of increased signal intensity. Based on known angiographic findings with fibrous metaphyseal defects, one may hypothesize that this is best explained by a hypervascularized area.

A cerebellar lesion was detected by ultrasonography (US) in a symptomatic newborn. Magnetic Resonance Imaging (MRI) demonstrated this lesion as a gyriform structure. Therefore a rare dysplastic gangliocytoma was suspected, which was compatible with histopathology. Immunohistochemical studies (monoclonal antibody Ki-67) showed signs of progression.

Juxta-articular osteoid osteomas as a cause of persistent pain of the shoulder, elbow and knee are presented basing on three own observations and a review of the literature. The sequence of the imaging examinations is equivalent to the osteoid osteomas in other localisations. CT permits a clear presentation of the nidus in the complex juxta-articular anatomy. Juxta-articular osteoid osteomas often show an absent or small perifocal osteosclerosis, whereas a laminar periosteal reaction was seen in all own cases.

Based on 57 fibrous metaphyseal defects the conventional radiologic signs are described as diagnostically reliable including asymptomatic patients as well as patients with a history of pain and lesions with positive scintigraphy. The radiologic morphology of the fibrous endosteal and medullary defects differs with the age of the patient. Beyond the age of 18 years there is a sclerosis of the lesion and a less marked arrosion of the corticalis. The differential diagnosis depends on the cortical, endosteal of medullary site of the fibrous defect as well as on the age of patient and includes the cortical metastasis, the juxta-articular osteoid-osteoma, the periosteal chondroma, the cortical irregularity, the solitary bone cyst, the fibrous dysplasia, the chronic osteomyelitis and the osteosclerotic osteosarcoma.

Based on 46 enosteal cartilaginous tumours of the long tubular bones (43 patients) the established radiological and Mirra's histopathological criteria of tumour status are assessed independently and compared retrospectively. In lesions of Lodwick's type I B (37 cases) with mineralisation of the cartilaginous matrix and facultatively cortical arrosion, lack of periosteal reaction, destruction of the corticalis and parosseal tumour extension none of Mirra's histopathological criteria of malignancy was found. It may be expected that biopsy and histopathological examination will not give valuable additional information in this radiological constellation, because there are no known definite histopathological criteria of benignity. Suspicious radiological findings should prompt complete resection of the lesion. Biopsy and histopathological classification are always crucial when matrix mineralisation is lacking and therefore the diagnosis of a cartilaginous tumour cannot be established radiologically.

Abdominal x-ray examinations represent a variety of indications with different demands on exposure latitude, contrast resolution and spatial resolution of screen-film system combinations. The diagnostic value of digital luminescent radiography (DLR) was thus compared to conventional x-ray examinations carried out with screen-film systems, speed class 200, by analysing matched digital and conventional exposures in 46 abdominal and 25 pelvic x-ray examinations in supine and left lateral view, 156 contrast examinations of the gastrointestinal tract, 140 excretory urographies, 8 cholecystographies, 22 lymphographies and in 6 phlebographies. The digital exposure dose was 50% of the conventional one. In DLR two differently post-processed images were obtained from one x-ray exposure: a display with low spatial frequency enhancement was processed to look like a conventional radiograph and was complemented by a display with high spatial frequency enhancement. Analysing the results statistically, DLR proved to be diagnostically equivalent to conventional radiography despite the reduction in exposure dose and the lower digital spatial resolution. Since high spatial frequency enhancement did not provide further diagnostic information and eventually resulted in border line artifacts, high spatial frequency enhancement is superfluous in abdominal x-ray examinations.

120 double-contrast barium enemas were obtained by both digital luminescent radiography (DLR) and conventional screen-film systems, the digital exposure dose being 50% of the conventional one. In DLR two differently post processed images were obtained from one x-ray exposure: a display with low spatial frequency enhancement was processed to look like a conventional radiograph and was complemented by a display with high spatial frequency enhancement. Analysing the results statistically DLR proved to be diagnostically equivalent to conventional radiography despite the reduction in exposure dose and a slightly diminished image quality. High spatial frequency enhancement did not provide further diagnostic information and is therefore superfluous in barium enemas.

A group of 59 patients with acute anterior uveitis (AAU) were examined for ankylosing spondylitis (AS) according to the New York criteria und criteria for early diagnosis of AS: 17/59 (29%) presented AS according to the New York criteria: a further 13/59 (22%) were classified as having incipient AS according to the early diagnosis criteria. These findings indicate that in a group of AAU patients there are, in addition to patients with definite AS, patients with initial AS though X-rays of the sacroiliac joints are still negative or equivocal. Early diagnosis criteria seem to be useful for identification of these patients at an early stage and can be used as a major selection criterion for monitoring programs.

Based on 7 of our own observations, the value of plain x-ray film of the abdomen, sonography, contrast medium diagnosis, and CT for diagnosing intramural haematomas of the colon is discussed.