Prognostic value of interim and restaging PET/CT in Hodgkin lymphoma. Results of the CHEAP (Chemotherapy Effectiveness Assessment by PET/CT) study - long term observation.

Very few studies have determined the prognostic value of interim and restaging PET/CT in patients with Hodgkin lymphoma using current standard of care therapy outside clinical trials. We analyzed the effect of the results of interim and restaging PET/CT on the survival (overall- and relapse-free) in patients who received standard first-line treatment based on the stage of disease and risk factors. We investigated the differences between the relapse and non-relapse groups based on the clinical pathological characteristics of patients who had positive interim PET/CT results.Between January 1, 2007 and December 31, 2011, the staging, interim and restaging PET/CT scans of patients with Hodgkin lymphoma were analyzed. The Deauville criteria were used for the evaluation of interim PET/CT scans. One hundred and thirteen Hodgkin lymphoma patients underwent staging, interim and restaging PET/CT scans. None of the therapy was modified based on the interim PET/CT results. The median follow-up time was 43.5 months. A total of 62 early stage patients and 51 advanced stage patients were identified. The five-year overall survival rates were 93.4% in the interim PET negative group and 58% in the interim PET positive group (p<0.001). The five-year relapse-free survival rates for the negative and positive groups were 92.7% and 40.8%, respectively (p<0.001). The negative predictive value was 100% in the early stage group and 82.35% in the advanced stage group. By comparison, the positive predictive values were 53.8% and 58.8%, respectively, in these two groups. In the interim PET positive group, patients over 40 years of age had a significantly higher probability of relapse (p=0.057).The routine clinical use of interim PET/CT is highly recommended based on our investigation. However, patients with positive interim PET/CT results required frequent additional evaluations.

Glucose-level dependent brain hypometabolism in type 2 diabetes mellitus and obesity.

BACKGROUND: Metabolic syndrome and its individual components lead to wide-ranging consequences, many of which affect the central nervous system. In this study, we compared the [18F]FDG regional brain metabolic pattern of participants with type 2 diabetes mellitus (T2DM) and non-DM obese individuals. METHODS: In our prospective study, 51 patients with controlled T2DM (ages 50.6 ± 8.0 years) and 45 non-DM obese participants (ages 52.0 ± 9.6 years) were enrolled. Glucose levels measured before PET/CT examination (pre-PET glucose) as well as laboratory parameters assessing glucose and lipid status were determined. NeuroQ application (NeuroQTM 3.6, Syntermed, Philips) was used to evaluate regional brain metabolic differences. [18F]FDG PET/CT (AnyScan PC, Mediso) scans, estimating brain metabolism, were transformed to MNI152 brain map after T1 registration and used for SPM-based group comparison of brain metabolism corrected for pre-PET glucose, and correlation analysis with laboratory parameters. RESULTS: NeuroQ analysis did not reveal significant regional metabolic defects in either group. Voxel-based group comparison revealed significantly (PFWE<0.05) decreased metabolism in the region of the precuneus and in the right superior frontal gyrus (rSFG) in the diabetic group as compared to the obese patients. Data analysis corrected for pre-PET glucose level showed a hypometabolic difference only in the rSFG in T2DM. Voxel-based correlation analysis showed significant negative correlation of the metabolism in the following brain regions with pre-PET glucose in diabetes: precuneus, left posterior orbital gyrus, right calcarine cortex and right orbital part of inferior frontal gyrus; whilst in the obese group only the right rolandic (pericentral) operculum proved to be sensitive to pre-PET glucose level. CONCLUSIONS: To our knowledge, this is the first study to perform pre-PET glucose level corrected comparative analysis of brain metabolism in T2DM and obesity. We also examined the pre-PET glucose level dependency of regional cerebral metabolism in the two groups separately. Large-scale future studies are warranted to perform further correlation analysis with the aim of determining the effects of metabolic disturbances on brain metabolism.

Combined prognostic value of absolute lymphocyte/monocyte ratio in peripheral blood and interim PET/CT results in Hodgkin lymphoma.

Decreased absolute lymphocyte/monocyte ratio (LMR) in peripheral blood has been reported as an unfavorable prognostic marker in Hodgkin lymphoma. We aimed to investigate whether combining LMR and interim PET/CT scan result (PET2) confers stronger prognostic value than PET2 alone. 121 HL patients were investigated. LMR was calculated from a blood sample taken at the time of diagnosis. PET2 was carried out after the second chemotherapy cycle. Survival was calculated using the Kaplan-Meier method and significance was determined by log-rank test. Effect of variants on survival results was examined using univariate and multivariate analyses. Best LMR cut-off value was determined by receiver operating characteristic (ROC) curve. Best LMR cut-off value was 2.11 in the case of our patients (LMR > 2.11: favorable, LMR ≤ 2.11: unfavorable). Overall and progression-free survivals (OS/PFS) were significantly worse both in lower LMR (≤ 2.11) (OS: P = 0.041, PFS: P = 0.044) and PET2 positive groups (OS: P < 0.001, PFS: P < 0.001). In PET2 positive patient group (n = 32) the low LMR result meant a significantly worse OS (0.030) and PFS (0.001). Both LMR and PET2 proved to be independent prognostic factors on multivariate analysis, and strengthened each other's effect.

Microcirculation of the fingers in Raynaud's syndrome: (99m)Tc-DTPA imaging.

AIM: We investigated the circulatory characteristics of patients suffering of primary and secondary Raynaud's syndrome. PATIENTS, METHODS: We examined 106 patients presenting with the classical symptoms of Raynaud's syndrom (47 primary, 59 secondary) by hand perfusion scintigraphy developed by our Department of Nuclear Medicine. After visual evaluation we analyzed the images semiquantitatively, using the finger to palm ratio. We statistically compared the patients with primary and those with secondary Raynaud's syndrome. RESULTS: By visual evaluation we constated regional perfusion disturbances in 42 from 59 patients with secondary Raynaud's syndrome. However, this was observed in only 3 from 47 patients with the primary form of this disease. This difference was statistically significant (p<0.001). Semiquantitative analysis showed that the finger/palm ratios (FPR) were significantly lower (p<0.05) for the patients with primary Raynaud's syndrome. No differences in the FPR values concerning sex or right and left side. CONCLUSION: The hand perfusion scintigraphy with (99m)Tc-DTPA is a noninvasive, cost effective diagnostic tool, which objectively reflects the global and regional microcirculatory abnormalities of the hands, and provides quantitative data for follow-up.

SPECT using 99mTc-DTPA for the assessment of disease activity in Graves' ophthalmopathy: a comparison with the results from MRI.

Currently available methods for the estimation of disease activity in the orbits of patients with Graves' ophthalmopathy (GO) have the disadvantages of being either expensive or time consuming. The aim of this study was to develop a quick, reliable method using Tc labelled diethylenetriaminepentaacetic acid (DTPA) and four-headed single photon emission computed tomography (SPECT) for this purpose. The theoretical basis of the method is that the high capillarization and oedema in the orbit may be reflected on Tc-DTPA images in GO. SPECT data of 28 orbits of 14 patients with GO were compared with magnetic resonance imaging (MRI) T2 relaxation time scores. Based on the number of 'active' muscles with T2 relaxation times of more than 70 ms in a given orbit, an MRI score of 0 (no active muscle) to 4 (all rectus muscles active) was assigned to the orbit. With MRI, 18 orbits were inactive, and 10 were active. Thirty minutes after the intravenous administration of 7 MBq.kg Tc-DTPA, 128 projections were acquired by a four-headed SPECT. On the sum of six transaxial slices containing the entire bulbar region of the skull, a triangle-like region of interest (ROI) was drawn (OR ROI). This ROI was 'slipped' to the right temporal region of the brain as reference site (B ROI). The count ratios of OR/B were calculated and compared to MRI score values. In the group of 18 inactive orbits (an MRI score of zero on both sides), in the transaxial plane, the mean OR/B value was 6.4+/-1.17, and in the group of 10 active orbits (an MRI score of 1-3) 8.30+/-2.08, the difference being significant (P <0.05). Tc-DTPA orbital SPECT is a promising method for the estimation of disease activity in the orbits of patients with Graves' ophthalmopathy.

The clinical usefulness of the fingers-to-palm ratio in different hand microcirculatory abnormalities.

A non-invasive nuclear medicine technique was developed to screen patients with painful hands so as to separate patients with a normal from those with an abnormal microcirculation of the hands in different clinical conditions. Such a technique is important, as the other methods available are either subjective or rather complicated. The study population consisted of 10 healthy individuals, 23 patients with Raynaud's syndrome and 15 patients with mixed connective tissue disease (MCTD). Sixty gamma-camera images of the hands (1 s each) were recorded after a bolus injection of 99Tcm-DTPA via a dorsal foot vein. Regions of interest were drawn on the summed images around the fingers and the palmar region. The fingers-to-palm ratio was then calculated from the total counts inside these regions of interest separately for each hand. The mean fingers-to-palm ratio was 0.94+/-0.18 (0.71-1.25) for the healthy group, 0.57+/-0.22 (0.21+/-1.11) for the MCTD group and 0.40+/-0.14 (0.18-0.77) for the Raynaud's patients. Analysis of variance showed these differences to be highly significant (P < 0.001). There were also significant differences between 6 MCTD patients in an active (mean 0.48) and nine patients in an inactive (mean 0.66) clinical state (two-sample t-test: P < 0.05). There were no significant differences between the fingers-to-palm ratios of the left and right hands of the same patients (one-sample t-test). Of the 23 primary Raynaud's patients, capillary microscopic data were pathological in only eight (34%). We conclude that our method is able to differentiate between patients with normal and those with abnormal microcirculation of the hands. Although measurement of the fingers-to-palm ratio is not a specific method, it is useful both for staging and in the follow-up of patients.

99m Tc-HMPAO labelled leukocyte scintigraphy in patients with rheumatoid arthritis: a comparison with disease activity.

The aim of this study was to test the applicability of 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) labelled leukocyte joint scintigraphy in the assessment of disease activity in 21 patients with rheumatoid arthritis, and to compare leukocyte scintigraphy with the Disease Activity Score (DAS), a validated activity index developed by the European League Against Rheumatism (EULAR). Twenty-one patients with rheumatoid arthritis were investigated by using 99mTc-HMPAO labelled leukocyte joint scintigraphy. The clinical and laboratory data were recorded, and the DAS was calculated and compared with the scintigraphic results in each case. A relatively high DAS score (4.71+/-1.07) was found in the majority of patients. The degree of accumulation of 99mTc-HMPAO leukocytes showed no correlation with a patient's age, gender, duration of disease, use of disease modifying anti-rheumatic drugs (DMARDs), visual analogue scale (VAS), Richie index, DAS, or any laboratory parameters. In contrast, a significant correlation was found between the global regional accumulation of the labelled leukocytes of the hands and feet, and the swollen-joint count. It is concluded that radiolabelled leukocyte scintigraphy could become one of the promising methods in the assessment of disease activity in patients with rheumatoid arthritis.

[Study of the contractility of the gallbladder by ceruletide infusion cholescintigraphy after litholysis]. / Az epehólyag-kontraktilitás vizsgálata köoldás után ceruletid infúziós cholescintigraphiával.

Twenty-six randomly selected patients 2-6 years (mean: 3.5) after rapid percutaneous catheteric litholysis at the Radiological Department were investigated by quantitative Ceruletide cholescintigraphy in this pilot study. The average EF of the patients with recurrent gallstones (Group II) was lower (55 +/- 23%) than that of the patients without stones (69 +/- 23%) (Group I). The authors conclude that this scintigraphic method could help not only to select the best method to make patient stonefree but has an important role in forecasting the prognosis of gallstone recovery after litholytic therapy.

[Fifteen years experience in the surgical treatment of primary hyperparathyroidism]. / Tizenöt év alatt szerzett tapasztalataink a primer hyperparathyreosis sebészi kezelésében.

We measured the efficacy of preoperative localization techniques and results of parathyroidectomy in patients with primary hyperparathyroidism (HPT). From 1986 to 2001, 92 patients were treated with primary HPT. Preoperative localization technique was used in all patients (US n = 85, Tc-99m-sestamibi/Tc-99m-pertechnetate subtraction scintigraphy n = 67, CT n = 18, MRI n = 14) to visualize the abnormal parathyroids. Results of localization studies were compared with surgical and pathological findings. Bilateral neck exploration was carried out in each patient for the identification of all parathyroid glands. If parathyroid adenoma was diagnosed, exstirpation of the abnormal parathyroid was performed. If diffuse hyperplasia was diagnosed, subtotal parathyroidectomy (3 1/2) was performed. The overall sensitivity was 94% for scintigraphy, 74% for US, 67% for CT and 50% for MRI. The PPV was 97% for scintigraphy, 92% for US, 100% for CT and for MRI. At surgery 66 patients had single adenomas and 3 patients had double adenomas. Diffuse hyperplasia was diagnosed in 21 and parathyroid carcinoma was found in 2 patients. Persistent HPT was noted in 1 patient. Recurrent HTP occurred 4 times. After a second operation their HPT disappeared. In conclusion, the sensitivity of Technetium-99m-sestambi and Technetium-99m-pertechnetate subtraction scanning was significantly superior compared to other localization methods. The use of these sensitive preoperative technique can improve the success rate, and decrease the incidence of persistent and recurrent HPT.

[The role of MIBI scintigraphy in the early detection of breast cancer]. / A MIBI szcintigráfia szerepe az emlórákok korai diagnosztikájában.

The authors investigate the role of MIBI scintigraphy in the early diagnosis of breast cancer. The importance of early diagnosis is emphasized by the fact that breast cancer has the highest morbidity and mortality preceding cervical carcinoma amongst women. Retrospective examinations were made in case of 42 patients operated before because of breast cancer in order to examine accuracy of both mammography and scintigraphy in comparison with the results of histological diagnosis. In these cases sensitivity of scintigraphy turned out to be 69%, while its specificity 42%. In cases of mammographical investigations the sensitivity proved to be 74% and specificity was 61%. Besides mammography, scintigraphy has a very important additional role in the diagnosis of breast cancer. Because of its results and costs scintigraphy is not able to take over the mammography's dominant position (as a popular diagnostic method) but in selected patients' groups it can help to realise tumors as well as to avoid unnecessary operations or needle biopsis. Based on our results this method can give significant additional information in T1b and especially in T1c states of tumors. Therefore this method can be offered as an additional investigation in cases of physically realised or mammographically screened, but not-palpable, larger than 1 cm size lumps when there is little or moderate risk of malignancy.

[Nuclear medicine in Europe: education]. / Nuklearmedizin in Europa. Die Ausbildungssituation.

The technical developments that have taken place in the preceding years (PET, hybrid imaging) have changed nuclear medicine. The future cooperation with radiologists will be challenging as well as positioning nuclear medicine in an European context. It can also be expected that education in nuclear medicine will undergo a harmonization process in the states of the European Union. In this paper, we describe how nuclear medicine education is organized in several European countries. We aim to stimulate constructive discussions on the future development of the specialization in nuclear medicine in Germany.

The value of 18-FDG PET/CT in early-stage breast cancer compared to traditional diagnostic modalities with an emphasis on changes in disease stage designation and treatment plan.

BACKGROUND: Proper preoperative staging is vital in the treatment of breast cancer patients. The aim of our study was to assess the value of the diagnostic information provided by PET/CT in surgical practice in breast cancer cases considered early-stage by conventional diagnostic modalities. METHODS: Whole-body 18-FDG PET/CT was performed on 115 breast cancer patients in whom traditional diagnostic modalities showed no signs of distant metastases or extensive axillary and/or extra-axillary lymphatic spreading, and the size of the primary tumor was <4 cm. RESULTS: The sensitivity of PET/CT in the detection of the primary tumor was 93%. The sensitivity of the traditional diagnostic modalities in the detection of multifocality was 43.8% while that of PET/CT was 100% (p < 0.001). In the assessment of axillary lymph nodes, ultrasound had a sensitivity of 30% and a specificity of 95%. The corresponding estimates for PET/CT were 72% and 96%, respectively. PET/CT detected distant metastases in 8 patients. TNM classification was modified after PET/CT scanning in 54 patients (47%). PET/CT data changed the treatment plan established upon the results of traditional imaging modalities in 18 patients (15.6%). CONCLUSIONS: PET/CT is able to assess primary tumor size and axillary lymphatic status more accurately than traditional diagnostic methods. It can detect distant metastases in 7-8% of those patients who were declared free of metastasis by clinical investigations. PET/CT scan modifies the disease stage determined by traditional diagnostic modalities in almost half of the patients and leads to a change in the treatment plan in every 6th patient.

Raynaud's syndrome: comparison of late and early onset forms using hand perfusion scintigraphy.

Primary Raynaud's disease is generally a disease of younger females; however, there are cases where symptoms present over the age of 40. These cases are described as late onset. In our current prospective study we compared the characteristics of early and late onset types of primary Raynaud's in 127 patients. In addition to the collection of medical records, we performed capillary-microscopy and hand perfusion scintigraphy using Tc-99 m DTPA to evaluate the microcirculation of each patient's fingers. Regarding the spectrum of the capillary-microscopic findings, we did not find any significant difference between the early and late onset forms. However, in hand perfusion examinations done using Tc-99 m DTPA, we measured a significantly lower finger/palm ratio (FPR) in the early onset group of patients. We also observed a correlation between the duration of the disease and the FPR, as well as between the age and FPR. Longer disease duration resulted in a significantly lower FPR. On the basis of our results, we believe that late onset Raynaud's should be treated as a separate entity. Due to its different characteristics found on examination and follow-up of our patients, functional hand perfusion examination should be recommended independently of the age-related characteristics of the disease.

Evaluation of interstitial lung disease in mixed connective tissue disease (MCTD).

OBJECTIVE: Interstitial lung disease (ILD) may be a characteristic, often serious, manifestation of mixed connective tissue disease (MCTD). In this retrospective study, the frequency and clinical picture of ILD were determined in patients with MCTD using two diagnostic tests: high-resolution computed tomography (HRCT) and inhaled aerosol clearance times of (99m)Tc-labelled diethylene-triamine pentaacetate ((99m)Tc-DTPA). In addition, pulmonary function, effects of therapy and a variety of immunoserological markers were also assessed. METHODS: One hundred and forty-four consecutive patients with MCTD were selected from the clinic, irrespective of the presence or absence of ILD. All patients underwent a detailed clinical assessment, chest HRCT scanning, chest radiography, inhaled aerosol of (99m)Tc-DTPA clearance times, and all pulmonary function tests. Patients who had active ILD received corticosteroid (CS) or CS in combination with cyclophosphamide (CPH). All investigations were repeated after 6 months of immunosuppressive therapy. RESULTS: Ninety-six out of 144 MCTD patients (66.6%) had active ILD, 75 of this group (78.1%) showed ground glass opacity, 21 patients (21.8%) ground glass opacity with mild fibrosis with HRCT. Forty-five patients with active ILD received 2 mg/kg/day CS for 6-8 weeks alone and 51 patients CS in combination with CPH (2 mg/kg/day). Six months later, after therapy, 67 out of 96 MCTD patients with ILD (69.8%) showed a negative HRCT pattern, ground glass opacity with mild fibrosis developed in 15 patients (15.6%), and fibrosis was detected in 13 patients (13.5%). Only one patient showed subpleural honeycombing. (99m)Tc-DTPA was rapid in all 96 MCTD patients with active ILD (28.7 +/- 8.2 min, normal value >40 min). After therapy the (99m)Tc-DTPA was normalized, 79 out of 96 patients (82.3%). Carbon monoxide diffusion capacity (DLCO) was reduced in 33 out of 96 MCTD patients with active ILD (34.3%), while there were no significant differences in the pulmonary function tests between the active versus inactive stage of ILD or versus patients without ILD. The sera of 96 MCTD patients with active ILD contained a high level of immune complexes (ICs), and the total haemolytic complement levels (CH50/ml U) decreased. After 6 months of therapy, the IC levels decreased and CH50/ml levels normalized (MCTD patients before and after active ILD: IC optical density = 355 +/- 227 vs 206 +/- 92, P<0.001; CH50/ml, 38.0 +/- 12.6 U vs 64.3 +/- 13.0 U, P<0.001). CONCLUSIONS: HRCT is the gold standard for diagnosis of ILD. However, we used another method, (99m)Tc-DTPA, in order to compare this technique with HRCT. This latter technique has not been studied previously in MCTD. The elevated levels of IC and increased complement consumption indicated that IC-mediated alveolocapillary membrane damage and tissue injury might play a role in the pathogenesis of ILD in MCTD.

Quantitative assessment of blood flow reserve using 99mTc-HMPAO in carotid stenosis.

Dynamic imaging of the inflow of technetium-99m hexamethylpropylene amine oxime (HMPAO) to the brain has been proved to allow estimation of the hemispherical cerebral blood flow (CBF) using the Patlak plot. In this study, we compared the hemispherical CBF (in ml/min/100 g) of different patient groups. A total of 25 patients (comprising 13 with migraine and 12 scheduled for endarterectomy owing to angiographically confirmed severe stenosis of the internal carotid artery on at least one side) underwent baseline and acetazolamide 99mTc-HMPAO brain perfusion studies. In addition, acetazolamide 99mTc-HMPAO studies were performed in 12 healthy subjects (no baseline study was performed for ethical reasons.) Dynamic studies were acquired by means of a dual-detector gamma camera with a large field of view (HELIX, Elscint). Special difference images were created to make definition of the aortic arch and hemispherical brain regions easier and more reproducible. A semi-automatic method was developed to determine the transit time from the aorta to the brain, making the generation of the Patlak plot even more robust. The baseline CBF values did not significantly depend on the disease (P>0.1), whereas the CBF values obtained after acetazolamide provocation did do so (ANOVA, P<0.001). Patients suffering from migraine showed a significant increase in global CBF values after acetazolamide provocation (paired t test, P<0.05), but we could not find any effect of the provocation in patients awaiting carotid endarterectomy, indicating a lack of cerebrovascular reserve capacity. Comparison of the results of the acetazolamide study in patients and the control group revealed the CBF values to be significantly lower in patients with carotid stenosis (two-sample t-test, P<0.001), but not in those with migraine (P>0.1). In summary, using quantitative analysis of 99mTc-HMPAO brain studies we could objectively compare the CBF of patients suffering from different diseases. Especially the CBF values obtained after acetazolamide provocation permitted effective differentiation of disease states. The quantitative results may be of assistance in therapy planning, e.g. in selection of the correct operative technique.