Positron emission tomography of incidentally detected small pulmonary nodules.

The aim of this study was to assess the value of fluorodeoxyglucose positron emission tomography (FDG PET) imaging of small pulmonary nodules incidentally detected by spiral computed tomography (CT) in a high-risk population. Ten patients (five females, five males, aged 54-72 years) were recruited from an ongoing 4-year placebo controlled intervention study of the effect of inhaled steroids in 300 smokers with moderate to severe chronic obstructive pulmonary disease. The participants received yearly CT scans of the chest. Patients with a negative chest radiograph at the time of inclusion, but with pulmonary nodules indeterminate for malignancy detected by conventional spiral CT on a subsequent scan, were referred for FDG PET. Histological diagnoses were sought for all nodules with FDG uptake or where CT showed that they had grown. Ten patients had pulmonary nodules indeterminate for malignancy (approx. 3.3% of the entire study population). The prevalence of malignancy in this group was 50%. The accuracy of PET was high, in spite of the fact that seven patients had nodules smaller than 15 mm and two patients had bronchoalveolar cell carcinoma. This small prospective study indicates that subsequent assessment with FDG PET of small pulmonary nodules incidentally detected by CT has the potential to minimize the numbers of invasive procedures performed in individuals with a benign pulmonary lesion. FDG PET also increases the possibility of an early diagnosis as compared to the strategy of watchful waiting.

Whole-body FDG-PET in patients with stage I non-seminomatous germ cell tumours.

Relapse occurs in 30% of patients with stage I non-seminomatous germ cell tumours (NSGCT) within 1 year after orchiectomy. Whole-body positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) may detect small metastases when standard staging with computed tomography (CT) and tumour markers is negative. In this study, 46 patients underwent FDG-PET after staging with normal CT and tumour markers. To exclude diagnostic test bias and workup bias, all patients had routine follow-up with repeated CT and tumour marker evaluation, even though the initial FDG-PET was positive. Thirty-six patients have remained disease free with a median follow-up of 48 months (range 24-76). Ten patients (22%) suffered disease relapse after a median of 2 months (range 1-8), and of these, seven had a true positive initial PET with increased uptake of FDG indicating metastatic disease. There were three false negative and no false positive PET scans. The sensitivity, specificity and accuracy of PET were 70%, 100% and 93%, respectively. The sensitivity of detecting small retroperitoneal metastases was 88%. The negative and positive predictive values were 92% and 100%, respectively, whereas the negative predictive value of standard staging procedures was 78%. FDG-PET thus seems to be superior to conventional staging (P=0.06) in stage I NSGCT. This non-invasive method may improve the overall management of patients with NSGCT.

Electrical admittance for filling of the heart during lower body negative pressure in humans.

To evaluate whether electrical admittance of intracellular water is applicable for monitoring filling of the heart, we determined the difference in intracellular water in the thorax (Thorax(ICW)), measured as the reciprocal value of the electrical impedance for the thorax at 1.5 and 100 kHz during lower body negative pressure (LBNP) in humans. Changes in Thorax(ICW) were compared with positron emission tomography-determined C(15)O-labeled erythrocytes over the heart. During -40 mmHg LBNP, the blood volume of the heart decreased by 21 +/- 3% as the erythrocyte volume was reduced by 20 +/- 2% and the plasma volume declined by 26 +/- 2% (P < 0.01; n = 8). Over the heart region, LBNP was also associated with a decrease in the technetium-labeled erythrocyte activity by 26 +/- 4% and, conversely, an increase over the lower leg by 92 +/- 5% (P < 0.01; n = 6). For 15 subjects, LBNP increased thoracic impedance by 3.3 +/- 0.3 Omega (1.5 kHz) and 3.0 +/- 0.4 Omega (100 kHz), whereas leg impedance decreased by 9.0 +/- 3.3 Omega (1.5 kHz) and 6.1 +/- 3 Omega (100 kHz; P < 0.01). Thorax(ICW) was reduced by 7.1 +/- 1.9 S. 10(-4) (P < 0.01) and intracellular water in the leg tended to increase (from 37.8 +/- 4.6 to 40.9 +/- 5.0 S. 10(-4); P = 0.08). The correlation between Thorax(ICW) and heart erythrocyte volume was 0.84 (P < 0.05). The results suggest that thoracic electrical admittance of intracellular water can be applied to evaluate changes in blood volume of the heart during LBNP in humans.

Experience in qualitative and quantitative FDG PET in follow-up of patients with suspected recurrence from head and neck cancer.

We evaluated positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in the detection of recurrent head and neck cancer, and compared visual and quantitative interpretation of PET images for their accuracy in the identification of tumour recurrence. Sixty-two FDG PET studies were performed in 56 patients having a total of 81 lesions, which were clinically suspected for recurrent carcinoma of the head and neck. The PET images were interpreted visually, and tracer uptake was quantitated as the standardised uptake value adjusted to body weight (SUV). Sensitivity of visual interpretation of the PET images for the presence of malignancy ranged from 84 to 95%, and specificity from 84 to 93%, respectively, depending on the selected scheme for grading of the lesions. Malignant lesions accumulated significantly more FDG than the benign ones (the median SUVs were 6.8 and 3.3, respectively, P<0.001). However, there was a wide overlap of the FDG uptake values between these two groups. Hence, the highest accuracy of quantitative analysis in correct identification of tumour recurrence (75% at Receiver Operating Curve analysis) was inferior to that of visual analysis (89%). FDG PET is feasible for the detection of recurrent head and neck cancer. Although quantitation of FDG uptake using SUV shows significantly higher tracer concentrations for malignant than benign lesions, the wide overlap of individual SUVs between these two groups is a serious concern in diagnostic evaluation. Therefore, in clinical practice it may be preferable to identify the presence of tumour recurrence within this patient group by qualitative interpretation of the PET images.

Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma.

Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty-eight patients with malignant melanoma of clinical stage II (local recurrence, in-transit and regional lymph node metastases) or III (metastases to other sites than in stage II) were included in the study. The results of the PET scans were compared with those obtained by clinical examination, computed tomography, ultrasound, radiography, and liver function tests and histology or clinical follow-up. With 18F-FDG PET we found for all foci a sensitivity of 97% and a specificity of 56%, compared with 62% and 22%, respectively, when using routine methods. For intra-abdominal foci, the sensitivity and specificity were 100% for both 18F-FDG PET and routine methods. Corresponding figures for pulmonary/intrathoracic foci were 100% and 33%, respectively. Of the patients included in this study, 34% would not have been staged correctly by conventional methods alone. We conclude from this study that 18F-FDG PET is a sensitive method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. 18F-FDG PET is useful as a supplement to clinical examination in melanoma staging.

4. Preliminary Findings of a Prospective Study of FDG-PET in Patients with Possible Lung Cancer.

Purpose: To examine the value of PET in diagnosis and staging of suspected lung cancer.Methods: 20 (13 male; mean age: 56 yr., range: 22-83 yr.) patients with chest X-ray findings suspicious of malignancy were staged a) "clinically" (X-ray, history/physical examination, lung function), b) by chest CT of thorax/upper abdomen, and c) by whole-body PET (GE Advance, visual analysis). The CT and PET studies were performed within 2 weeks of admission and read blinded to all information except the chest X-ray report. The decision to refer to mediastinoscopy/thoracotomy was made by a tumor board using clinical information, CT and PET findings. In principle, suspected metastatic lesions were biopsied before surgery. The gold standard was histology from biopsy or thoracotomy, or resolution of the X-ray findings and symptoms.Results: One patient was excluded because of uncertain diagnosis. In 3 (15%) patients surgery was avoided mainly because of the PET findings. In one SCLC patient and one lymphoma patient, PET showed extensive disease, which changed the chemotherapy regime. Accuracy was 83% for clinical stage, 79% for CT and 77% for PET. Four (20%) false positive PET findings were caused by granuloma, pneumonia and BOOP. These nodules were only 1 to <3 cm, while malignant nodules were 2-8 cm. There were no false negative PET or CT studies.Conclusion: FDG-PET is valuable in patients suspected for pulmonary malignancy, since thoracotomy was avoided in 15% of patients and in 10% of patients more extensive disease was found which changed the chemotherapy regime.

18F-FDG whole body positron emission tomography (PET) in patients with unknown primary tumours (UPT).

The management of patients with unknown primary tumours (UPT) often includes a large number of radiographical studies and invasive procedures, but the occult primary tumour is detected in less than 25%. In this prospective study we explored whether non-invasive whole body PET scans using FDG (18-F-fluorodeoxyglucose) are of clinical value in detection of UPT. Whole-body FDG-PET scans were performed in 20 patients following standard staging procedures according to histology. PET results were verified either histologically or by the clinical course of the disease. 11 patients had neck metastases (5 squamous cell, 5 adenocarcinomas and 1 poorly differentiated carcinoma). The remaining patients had metastases located in bone (3), bone marrow (1), brain (1), pericardium (1), skin (1), pleura (1) and chest wall (1). All metastatic lesions were visible with PET. In 13 patients PET suggested the site for the primary tumour and this was verified in 9 (45%), either histologically or by the clinical course of disease. 8 of these had primary lung cancer and 1 had carcinoma at the basis of the tongue. In most patients PET had no treatment related implications. 3 patients with non-small cell lung cancer (NSCLC) received chemotherapy prompted by the PET result. The rest received either radical radiotherapy to the head and neck region (7), palliative radiotherapy to the metastatic lesion (8), chemotherapy based on signet ring cell carcinoma in bone marrow (1) or no therapy (1). These results indicates that PET is useful in UPT preceding expensive and invasive diagnostic procedures and can result in a faster diagnosis in approximately one third of the patients who then avoid unnecessary extensive procedures. Furthermore, a larger proportion of patients will receive treatment aimed at the correct diagnosis. A prospective cost-effectiveness analysis of PET in this setting is warranted.

[Sentinel node diagnostics in malignant melanoma]. / "Sentinel node"-diagnostik ved malignt melanom.

New trial have shown that immediate regional lymph node dissection offers increased survival in patients with regional lymph node metastases only. Introduction of isotope technique to identify the first node, the sentinel node (SN), receiving lymph from a tumour area has made it possible to avoid node dissection in SN metastasis negative patients. The feasibility of the technique is illustrated by to examples.

[FDG-PET in the staging of malignant melanoma]. / FDG-PET til udredning af malignt melanom.

Positron emission tomography (PET scanning) is a useful tool in staging of malignant melanoma. A radiolabelled glucoseanalogue can demonstrate changes in metabolism and thus identify malignancy in macroscopic unchanged structures. It is a non-invasive, fast method to identify especially visceral, still symptomless metastases. The patient can often be spared from mutilating surgery.

Nuclear 3,5,3'-triiodothyronine receptor binding in mononuclear blood cells from patients with malignant blood diseases and small cell carcinoma of the lung.

We have previously demonstrated enhanced daily turnover of thyroid hormones in patients with hypermetabolic symptoms due to malignant haematologic disorders or small cell carcinoma of the lung. We hypothesized that some of these symptoms might be due to enhanced peripheral effects of T3. We therefore studied the nuclear T3 receptor binding in circulating mononuclear blood cells in 5 patients with malignant haematologic disorders, 5 with untreated small cell carcinoma of the lung, and 11 healthy controls. Maximal binding capacity of T3 (MBC) was increased 2.5 times in the diseased patients, (median (range)) 110 fmol/mg DNA (75-519) in the haematologic group (p < 0.01), 106 fmol/mg DNA (47-490) (p < 0.10) in small cell carcinoma patients, as compared to 43 fmol/mg DNA (26-94) in controls. The affinity constant Ka of bound T3 was reduced to one-third in the diseased patients. No differences were found between serum thyroid hormone or TSH levels. It is hypothesized, that previously demonstrated enhanced turnover of thyroid hormones in these states of disease might in part be due to increased peripheral consumption of thyroid hormones, including enhanced receptor binding of T3.

[Hypophyseal hyperthyroidism. Non-tumoral hypersecretion of thyroid stimulating hormone with clinical hyperthyroidism]. / Hypofysaer hypertyreose. Ikke-tumorbetinget hypersekretion af thyroideastimulerende hormon med klinisk hypertyreose.

A case of hyperthyroidism due to inappropriate TSH secretion in a 45-year-old man is presented. The diagnosis was confirmed by measurement of increased serum TSH values using three different assays, increased T4 and T3 values, the clinical picture, and the effect of anti-thyroid treatment. Nuclear magnetic resonance and computerized tomographic scans of the pituitary fossa showed no abnormalities. Treatment with long-term oral thyrotropin-releasing hormone, oral triiodothyronine, and short-term subcutaneous Sandostatin injections resulted in partial suppression of TSH without however adequate clinical effect. Treatment with thyroxin, bromocriptine, and triiodothyroacetic acid did not alter the parameters. It is concluded, that the inappropriate TSH secretion may be due to a pituitary microadenoma.

[Severe adverse effects of low-dose carbimazole treatment in hyperthyroidism. A retrospective study of 476 patients]. / Alvorlige bivirkninger ved behandling af hypertyreose med karbimazol i lav dosering. En retrospektiv undersøgelse af 476 patienter.

A material of 476 hyperthyroid patients treated with carbimazole and 69 patients treated with PTU in the period from 1978 to 1986 were studied retrospectively. The antithyroid treatment was given in low dosage without supplementary thyroxine. The total frequency of adverse effects, defined as symptoms leading to discontinuance of the treatment, was 8.0% for carbimazole and 2.9% for PTU. There were no cases of agranulocytosis in the group treated with carbimazole, and one case in the group treated with PTU. No relationship between age and adverse effects could be demonstrated. The relationship between adverse effects and dosage is discussed, and it is concluded that low dosage treatment with carbimazole has a very low frequency of adverse effects in terms of agranulocytosis and toxic hepatitis.