Ecotoxicological risk of pharmaceuticals from wastewater treatment plants in Korea: occurrence and toxicity to Daphnia magna.

The overall ecotoxicological effect of pharmaceutically active compounds (PhACs) detected in the effluents of Korean wastewater treatment plants (WWTPs) to Daphnia magna was investigated using biological and chemical analyses. The bioassay results showed median lethal concentrations and no-observed-effect concentrations ranging from a few to tens of ppm levels for nine PhACs in 48-h acute and 21-d chronic tests. The mixture effects of pharmaceuticals also were examined by other acute and chronic tests, which showed no significant toxicity despite a slightly increased combined effect of approximately twofold. The residual concentrations of nine PhACs were analyzed at concentrations ranging from 10 ng/L to 89 microg/L in the influents and from 10 ng/L to 11 microg/L in the effluents from four metropolitan cities in South Korea between January and November of 2004. Through repeated investigations of the influents and the effluents from different WWTPs, relatively higher removal efficiencies (23.9-91.3%) compared with those of previous surveys performed in other countries were observed for most pharmaceuticals, with the exception of acetaminophen (8.7%). The present study showed no significant risk effects of the effluents from WWTPs containing pharmaceuticals (i.e., hazard quotient < 1), even at the 95th percentile contamination range, although a risk assessment factor of 1,000 was applied. Therefore, it can be concluded that the potential risk of pharmaceuticals should be monitored carefully with more bioassay data, because many uncertainties still exist in the determination and toxicity of metabolites in water environments. No significant risk was observed, however, from the selected PhACs in the effluents from WWTPs discharged into surface waters.

Radioisotope-guided surgery in patients with pheochromocytoma and recurrent medullary thyroid carcinoma: a comparison of preoperative and intraoperative tumor localization with histopathologic findings.

BACKGROUND: The objective of this study was to appraise the detection of metastases of medullary thyroid carcinoma (MTC) and pheochromocytoma using radioguided surgery (RGS) and to compare the results with external imaging modalities, surgical palpation, and histopathologic findings. METHODS: Twenty-five patients with recurrent MTC underwent preoperative scintigraphic imaging with 500 megabecquerels (MBq) of technetium 99m(V)-dimercaptosuccinic acid [(99m)Tc(V)-DMSA] and 222 MBq of indium 111 ((111)In)-pentetreotide. The radiopharmaceutical that showed the greatest preoperative tumor uptake was selected for intraoperative RGS. Surgery was performed 24 hours after the administration of (111)In-pentetreotide or 4 hours after the injection of (99m)Tc(V)-DMSA. Furthermore, three male patients underwent surgery who suffered from recurrent pheochromocytoma (injection of 180 MBq iodine 123-labeled metaiodobenzylguanidine [(123)I-MIBG] 4--5 hours before surgery). RESULTS: Overall, lesion detection sensitivities in patients with MTC for computed tomography, (111)In-pentetreotide, and (99m)Tc(V)-DMSA were 32%, 34%, and 65%, respectively. Surgical palpation identified lymph node metastases of recurrent MTC with a sensitivity of 65%, whereas RGS localized 64 malignant lesions (sensitivity, 97%). Altogether, 71 lesions could be excised, 5 of which were adjudged false positive with respect to MTC metastases. Both surgical palpation and RGS localized all paravertebral subdiaphragmatic lesions (size > or = 2 cm) of recurrent pheochromocytoma seen in the preoperative MIBG scan. CONCLUSIONS: RGS was capable of localizing more and smaller metastases of MTC compared with conventional imaging modalities and surgical palpation. However, the relatively high radioligand accumulation in the kidneys ((111)In-pentetreotide) and the dense hepatic and biliary signals using MIBG limited their use for intraoperative detection of tumors in the area of the adrenal gland.

Positron emission tomography (PET) for staging and evaluation of response to treatment in patients with Hodgkin's disease.

Forty two examinations utilizing F-18 FDG-PET were performed in 23 patients with Hodgkin's disease to study for involved lymphoma regions and compared to conventional staging procedures. Twenty stagings were performed at diagnosis of untreated Hodgkin's disease or at first relapse, and 22 restagings during and after chemoradiotherapy. At diagnosis in 5 of 20 patients PET and other procedures revealed different extranodal manifestations and in 3 patients established different clinical staging. PET seemed to be accurate in the assessment of lymphoma involvement in nodal sites. During follow up, in 10 out of 22 investigations different results and discrepancy were recorded, mostly due to the different extent of F-18-FDG metabolism in residual masses in lymphatic tissues compared to CT, X-ray or ultrasonography. The results indicate that PET may have advantages in the assessment of remissions in nodal sites. Less conclusive results were observed with regard to extranodal involvement or inflammatory disease. In conclusion PET may be sufficient for the staging of the majority of patients with Hodgkin's disease and particularly for assessing remission status in nodal sites, but PET may have disadvantages in the evaluation of extranodal lymphoma and inflammatory disease.

Diagnostic accuracy and predictive value of the tumor-associated antigen S100 in malignant melanomas: validation by whole body FDG-PET and conventional diagnostics.

UNLABELLED: We investigated the predictive value of the protein S100 as a tumor-marker in the post-surgical follow-up staging of patients with High Risk melanomas (Clark Levels IV/V, Thickness > 0.75 mm). METHODS: In 51 follow-up studies, performed in 50 patients, serum concentrations of the protein S100 were measured and evaluated with respect to their diagnostic value based on the findings of whole body F-18-FDG-PET studies. The findings of FDG-PET were correlated with the findings of CT, MRI, lymph node sonography, bone scintigraphy, and with histological findings, or a follow-up staging after at least 6 months, respectively. Thus, FDG-PET exhibited a sensitivity of 100% and a specificity of 95%. S100 concentrations were measured by an established RIA (Ria-mat Sangtec 100) and by a novel LIA (Lia-mat Sangtec 100 beta). Subsequently, S100 was compared with thymidine kinase for the predictive values of both tumor-markers in the follow-up of malignant melanoma. RESULTS: Intraindividual comparison of S100 concentrations measured by LIA with those obtained by RIA showed a calculated correlation coefficient of 0.97 (Cutoff-levels were 0.1 microgram/l [RIA] and 0.2 microgram/l [LIA]). The arrangement of these cutoff-levels leads to a sensitivity of 85% at a specificity of 55% for Protein S100 when measured by RIA, and to a sensitivity of 77% at a specificity of 61% when measured by LIA. The negative predictive values are 91% (RIA) and 88% (LIA), in association with positive predictive values of 39% (RIA) and 40% (LIA). At a cutoff-level of 4.0 micrograms/l, thymidine kinase showed a sensitivity of 70% and a specificity of 41%. CONCLUSIONS: a) The results obtained by LIA are in a very good correlation with the results measured by the well-established RIA. Thus, the LIA is a suitable method for the clinical routine. b) The protein S100 as a tumor-marker of malignant High Risk melanomas has no clinically important sensitivity and specificity as could be proved by a comparison with the predictive value of FDG-PET. c) Whether or not during therapy information concerning progression/remission of the disease can be received out of repetitive measurements of the S100, has to be shown by the results of validated long term follow-up studies.

Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease.

In a case of Huntington's disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patient's performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders.

Metabolic (PET) and receptor (SPET) imaging of well- and less well-differentiated tumours: comparison with the expression of the Ki-67 antigen.

[111In-DTPA-D-Phe1]-pentetreotide has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased FDG uptake is associated with malignancy. This prospective study explores the role of metabolic (PET) and receptor (SPET) imaging in well- and less well-differentiated tumours--gastroenteropancreatic (GEP) tumours, medullary thyroid carcinomas (MTC) and thymic carcinomas--in comparison with the expression of the Ki-67 antigen. Ten patients with GEP tumours, five with MTC and five with thymic carcinomas were studied. Prior to PET, somatostatin receptor scintigraphy (SRS) was performed in all patients. Sixty minutes after the intravenous administration of 18F-FDG (370 MBq), whole-body PET was performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). Preoperative SRS detected multiple primary tumours and metastatic lesions in four patients with well-differentiated carcinoids (low Ki-67 expression). Whole-body PET demonstrated normal distribution of FDG in all of these patients. In patients with recurrent MTC and rapidly increasing CEA levels, SRS showed no in vivo somatostatin receptor expression, whereas whole-body PET localized 24 locoregional lymph node metastases with increased FDG uptake. Immunocytochemistry of the resected lymph nodes demonstrated high Ki-67 expression associated with a high proliferative activity. Similar results in receptor scintigraphic and metabolic behaviour were obtained from patients with metastasizing thymic carcinomas (high Ki-67 expression). In conclusion, SRS has been shown to localize well-differentiated GEP tumours. In contrast, FDG PET is only valuable for predicting malignancy in less well-differentiated GEP tumours and malignant MTC associated with rapidly increasing CEA levels. Therefore, an additional 18F-FDG PET procedure should only be performed if SRS is negative. Furthermore, our preliminary results suggest that increased FDG metabolism reflects the invasiveness of thymic carcinomas.

Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease.

In a case of Huntington's disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patient's performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders.

[Long-term follow-up and therapeutic control of a hepatic metastatic acinar cell carcinoma of the pancreas using FDG PET]. / Langzeitverlaufs- und Therapiekontrolle eines hepatisch metastasierenden Azinuszellkarzinoms des Pankreas mittels FDG-PET.

A 33 years old woman presented with cramp-like abdominal pain. Ultrasound examination revealed multiple lesions in the liver of hyper- and hypoechoic echogenicity which in accordance to subsequently performed computed tomography and dynamic hepatobiliary scintigraphy were considered to be a focal nodular hyperplasia (FNH). A severe increase of the serum lipase concentration, suspected to be an acute pancreatitis, was treated conservatively and led to a short improvement of symptoms. Some months later, a severe progression of the pain symptoms occurred, along with a measurable expansion of the abdominal circumference and palpable tumors of the liver. The dynamic hepatobiliary imaging and the static liver scan showed a decreased perfusion and function of the nodes as well as a reduced RES activity, respectively. A subsequently performed Positron Emission Tomography (PET) with F-18-Fluorodeoxyglucose (FDG) showed a massively increased glucose metabolism of the liver tumors. The histologic result of several biopsies of the tumors revealed metastases of an acinus cell carcinoma of the pancreas. Under systemic and local chemotherapy, a temporary remission could be obtained that was clearly detectable in a second FDG-PET. Nevertheless, during the further course of the disease, a progression occurred being detectable in an additional control PET-study by an increase in tumor size as well as in tumor glucose metabolism. The patient died in liver coma 15 months after the histologic diagnosis was obtained.

Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer.

The aims of this study were to investigate the detection of cervical lymph node metastases of head and neck cancer by positron emission tomographic (PET) imaging with fluorine-18 fluorodeoxyglucose (FDG) and to perform a prospective comparison with computed tomography (CT), magnetic resonance imaging (MRI), sonographic and histopathological findings. Sixty patients with histologically proven squamous cell carcinoma were studied by PET imaging before surgery. Preoperative endoscopy (including biopsy), CT, MRI and sonography of the cervical region were performed in all patients within 2 weeks preceding 18F-FDG whole-body PET. FDG PET images were analysed visually and quantitatively for objective assessment of regional tracer uptake. Histopathology of the resected neck specimens revealed a total of 1284 lymph nodes, 117 of which showed metastatic involvement. Based on histopathological findings, FDG PET correctly identified lymph node metastases with a sensitivity of 90% and a specificity of 94% (P<10(-6)). CT and MRI visualized histologically proven lymph node metastases with a sensitivity of 82% (specificity 85%) and 80% (specificity 79%), respectively (P<10(-6)). Sonography revealed a sensitivity of 72% (P<10(-6)). The comparison of 18F-FDG PET with conventional imaging modalities demonstrated statistically significant correlations (PET vs CT, P = 0.017; PET vs MRI, P = 0.012; PET vs sonography, P = 0.0001). Quantitative analysis of FDG uptake in lymph node metastases using body weight-based standardized uptake values (SUVBW) showed no significant correlation between FDG uptake (3.7+/-2.0) and histological grading of tumour-involved lymph nodes (P = 0.9). Interestingly, benign lymph nodes had increased FDG uptake as a result of inflammatory reactions (SUVBW-range: 2-15.8). This prospective, histopathologically controlled study confirms FDG PET as the procedure with the highest sensitivity and specificity for detecting lymph node metastases of head and neck cancer and has become a routine method in our University Medical Center. Furthermore, the optimal diagnostic modality may be a fusion image showing the increased metabolism of the tumour and the anatomical localization.

Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings.

Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node metastasis located in the upper mediastinum. Somatostatin receptor scintigraphy only demonstrated tumour sizes more than 1 cm in diameter. These preliminary results suggest that the combination of metabolic [99mTc(V)-DMSA] and receptor ([111In-DTPA-D-Phe1]-pentetreotide) imaging is more sensitive for tumour localization in patients with recurrent MTC than the use of only one radiopharmaceutical. However, neither 99mTc(V)-DMSA nor [111In-DTPA-D-Phe1]-pentetreotide is specific for MTC and false-positive scintigraphic findings have to be considered. Furthermore, somatostatin receptor scintigraphy cannot visualize small tumour sites (<1 cm). Further studies are needed to evaluate the role of combined metabolic and receptor imaging in the management of patients with recurrent MTC.

[Value of 18F fluorodeoxyglucose positron emission tomography in radiotherapy planning of head-neck tumors]. / Stellenwert der 18F-Fluordeoxyglucose-Positronenemissionstomographie in der Radiotherapieplanung von Kopf-Hals-Tumoren.

PURPOSE: An individualized radiation treatment planning in patients with head and neck tumors requires an exact definition of tumorspread. Despite of high reliability of methods like computed tomography, sonography or magnetic resonance imaging used in daily routine, the correct diagnosis of lymphonodal tumor infiltration is often not possible. In a prospective trial, we examined whether an additional FDG-PET gives a relevant gain of information for radiation treatment planning. PATIENTS AND METHODS: We studied data of 34 patients with histologically confirmed squamous cell carcinoma of the head and neck who received a FDG-PET prior to treatment planning additionally to conventional staging procedures. The extent of changes of treatment strategy or target volume due to additional FDG-PET findings were analyzed. RESULTS: In 9/22 of patients with primary tumors and in 7/12 of patients with recurrent disease, FDG-PET detected additional tumor manifestations. In all cases, changes of treatment strategy or target volume were necessary. Regarding patients with primary tumors, the percentage of treatment modifications was highest in patients with large tumors (T3 and T4) and patients with advanced lymph node involvement (N2 and N3). CONCLUSIONS: Especially in patients with recurrent disease and patients with advanced tumor stages, FDG-PET is able to give clinically relevant information compared to conventional staging procedures. Therefore, in these group of patients a FDG-PET study prior to radiotherapy planning should be considered.

Intraoperative gamma probe detection of neuroendocrine tumors.

UNLABELLED: Previous studies of the intraoperative use of a handheld gamma probe to localize metastases and primary tumors of colorectal cancer have shown improved assessment of tumor spread and changes in surgical management based on added information gained by radioimmunoguided surgery. We conducted a prospective study to determine whether intraoperative radiodetection is able to reveal microscopic and occult disease of neuroendocrine tumors [medullary thyroid carcinomas (MTCs), gastroenteropancreatic (GEP) tumors]. METHODS: After the injection of 180 MBq [111In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe1]pentetreotide and/or 500 MBq 99mTc-dimercaptosuccinic acid (DMSA) (both for double-nuclide scintigraphy), preoperative somatostatin receptor imaging (12 patients with GEP tumors) and double-nuclide scintigraphy (10 patients with relapsing MTCs were performed. The results were combined with the information obtained from conventional imaging modalities (CT and sonography). Intraoperative radiodetection was performed 24 hr after administration of [111In-DTPA-D-Phe1]pentetreotide or 4 hr after the injection of 99mTc-DMSA using a handheld gamma probe. RESULTS: Intraoperative gamma counting localized 70 somatostatin receptor-positive lesions of GEP tumors, whereas preoperative receptor imaging visualized 74%, surgical palpation visualized 44% and radiological imaging modalities localized only 43%. In 10 patients with recurrent MTCs, the surgeon was successful in localizing and removing 30 tumor lesions using the gamma probe. Twenty-seven of 30 lesions demonstrated tumor involvement, whereas 3 lesions were false-positive (lymphadenitis). Double-nuclide scintigraphy revealed 67% (Octreoscan, 7 of 20; 99mTc-DMSA, 13 of 20), surgical palpation revealed 60% and conventional imaging methods (CT, sonography) revealed only 50% of all lesions detected intraoperatively by the handheld gamma probe. The smallest lesion identified by the handheld probe (not palpated by the surgeon) was a lymph node metastasis (5-mm diameter). CONCLUSION: The preliminary data show that intraoperative handheld gamma probe detection of microscopic and occult endocrine tumors is feasible and more sensitive than external scintigraphy and conventional imaging.

Primary staging and follow-up of high risk melanoma patients with whole-body 18F-fluorodeoxyglucose positron emission tomography: results of a prospective study of 100 patients.

BACKGROUND: Positron emission tomography (PET) has been retrospectively reported to be a sensitive method for detecting malignant melanoma metastases. METHODS: One hundred consecutive patients with high risk melanoma (tumor thickness > 1.5 mm) were prospectively evaluated (52 at primary diagnosis, comprising Group A, and 48 during follow-up, comprising Group B) by whole-body PET and conventional diagnostics (CD). RESULTS: In Group A, the sensitivity of PET was 100% and the specificity was 94%, whereas CD did not identify any of the 9 lymph node metastases and demonstrated a lower specificity (80%). In Group B, 121 lesions were detected, 111 by PET and 69 by conventional imaging. On the basis of patients, the sensitivity, specificity, and accuracy of PET were 100%, 95.5%, and 97.9%, respectively (91.8%, 94.4%, and 92.1%, respectively, on the basis of single metastases). Prospectively, CD did not identify all patients with progression (sensitivity, 84.6%) and detected significantly fewer metastases (sensitivity, 57.5%) with much lower specificity (68.2% on the basis of patients, 45% on the basis of single lesions); therefore, the accuracy of CD was 77.1% on the basis of patients and only 55.7% on the basis of single metastases. Results also depended on specific sites: while PET yielded a higher sensitivity in detecting cervical metastases (100% vs. 66.6%) and abdominal metastases (100% vs. 26.6%), computed tomography proved to be superior in detecting small lung metastases (87% vs. 69.6%). CONCLUSIONS: PET is a highly sensitive and specific technique for melanoma staging. With the exception of the brain, one single whole-body 18F-fluorodeoxyglucose-PET scan could replace the standard battery of imaging tests currently performed on high risk melanoma patients.

[Combined arthroscopic and radiation synovectomy in rheumatoid arthritis]. / Synovektomie und Synoviorthese als Kombinationstherapie bei rheumatoider Arthritis.

In rheumatoid arthritis of the knee joint good results are obtained using arthroscopic synovectomy or radiation synovectomy. Aim of our study was to investigate, whether the combination of these two minimal invasive interventions achieves better results. First we performed arthroscopic synovectomy of the knee joint followed by radiation synovectomy with application of 111-222 MBq Yttrium-90 6 weeks later. In a prospective randomised clinical trial between 1987 and 1991 we performed radiation synovectomy on 22 knee joints and combined arthroscopic and radiation synovectomy on 26 knee joints. We explored the patients preoperatively, 6 weeks and 6 months postoperatively. In 1996 we evaluated 141 knee joints in a retrospective clinical trial. 90 Knee joints had been treated with the combined therapy, 39 only with radiation synovectomy and 12 only with arthroscopic synovectomy. Depending on the three different therapeutic interventions, the patients were classified into midterm (3-5 years) and long-term (6-8 years) observation groups. The trials are based on the standardized ARO-Questionnaire of the knee joint, the modified ARO Knee-Score and the radiological grading according to Larsen, Dale and Eek. In the prospective clinical trial we found significant better results for patients treated with the combined therapy than for patients treated with radiation synovectomy only regarding the parameter swelling, effusion, range of motion, pain and Knee-Score. In the long-term results of the retrospective clinical trial the patients treated with the combined therapy showed a significant better outcome for the parameters pain, swelling and Knee-Score, than the patients treated with radiation synovectomy. Although no statistically significant difference was found comparing the results of the combined therapy with arthroscopic synovectomy, an improvement of the clinical outcome can be observed performing arthroscopic synovectomy followed by radiation synovectomy. In the treatment of rheumatoid arthritis of the knee joint a better outcome is achieved performing combined arthroscopic and radiation synovectomy than performing only one of the methods.

Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours.

Scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide or pentavalent technetium-99m-dimercaptosuccinic acid [99mTc(V)-DMSA] has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased fluorodeoxyglucose (FDG) uptake is associated with malignancy. The aim of this study was to compare the value of fluorine-18 FDG positron emission tomography (PET) with that of somatostatin receptor scintigraphy (SS-R) and dual-radionuclide scintigraphy [SS-R and 99mTc(V)-DMSA = DNS] in detecting malignant neuroendocrine tumours. Fifteen patients with metastasizing gastroenteropancreatic tumours (GEP tumours; n = 7), medullary thyroid carcinomas (MTCs; n = 8) and elevated tumour markers [GEP tumours: 5-hydroxyindoleacetic acid, insulin; MTCs: calcitonin, carcinoembryonic antigen (CEA)] were studied. Prior to PET, all patients with GEP tumours underwent SS-R. DNS was performed in all patients with MTC. Patients had been fasting for at least 12 h and normal glucose plasma levels were confirmed. Sixty minutes after intravenous administration of 18F-FDG (mean: 374 MBq) whole-body PET and regional scans were performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). In two patients with less-differentiated GEP tumours associated with high proliferative activity and increased FDG uptake, SS-R failed to detect any lesion. In comparison, in four patients with well-differentiated GEP tumours showing low proliferative activity, SS-R localized four primary tumours, 22 lymph node metastases and 18 malignant liver lesions, whereas 18F-FDG PET demonstrated normal distribution. In one patient with a metastasizing carcinoid (medium proliferative activity) SS-R localized multiple metastases, whereas PET demonstrated low FDG uptake in all known metastases. In patients with recurrent MTC and rapidly increasing CEA levels DNS detected only three lesions in two patients, whereas PET demonstrated one pulmonary, three osseous, 20 mediastinal, ten locoregional, and four liver metastases in seven patients. Twenty-nine malignant lesions were confirmed by follow-up and nine lymph node metastases could be surgically removed. In conclusion, PET imaging of gastroenteropancreatic tumours revealed increased glucose metabolism only in less-differentiated GEP tumours with high proliferative activity and metastasizing MTC associated with rapidly increasing CEA levels. Therefore, additional 18F-FDG PET should be performed only if SS-R or DNS is negative.

Prognostic significance of coronary flow reserve on left ventricular ejection fraction in cardiac transplant recipients.

BACKGROUND: Cardiac allograft vasculopathy is a common phenomenon in epicardial and microvascular vessels. Intramyocardial vessel disease may lead to small, stellate infarcts. The present study tested the impact of microvascular vasomotor function on changes in left ventricular systolic function in the long-term follow-up after cardiac transplantation. METHODS: Seventeen consecutive cardiac transplant patients, 40+/-21 months after cardiac transplantation, without angiographically visible cardiac allograft vasculopathy and without episodes of acute rejection were included in the study. Coronary microvascular reactivity was assessed by the endothelium-dependent stimulus acetylcholine (50 microg i.c.) and by the endothelium-independent stimulus dipyridamole (0.56 mg/kg i.v.) utilizing an Doppler catheter. Radionuclide ventriculography was performed at the time of coronary flow measurement and repeated 2 years later to correlate changes in left ventricular ejection fraction with the coronary flow reserve measurement 2 years previously. RESULTS: There was a statistically significant correlation between endothelium- independent coronary flow reserve to dipyridamole and changes in ejection fraction at rest (r=0.59; P < 0.01) and during exercise (r=0.48; P < 0.05). Twenty-four months later, patients with a coronary flow reserve to dipyridamole < 2.5 showed a significant decline in ejection fraction during exercise (-7 +/- 5%) compared to patients with a coronary flow reserve > 2.5 (1.1+/-5%; P=0.003). Coronary flow reserve to acetylcholine was not correlated with a reduced ejection fraction during exercise. CONCLUSIONS: Endothelium-independent microvascular dysfunction has prognostic importance for deterioration of left ventricular function in cardiac transplant recipients without angiographically visible coronary artery stenoses. These results reinforce the concept that microvascular and epicardial vessel disease after transplantation are two distinct entities with different functional consequences.

Gated metabolic positron emission tomography (GAPET) of the myocardium: 18F-FDG-PET to optimize recognition of myocardial hibernation.

The aim of this study was to test the feasibility of the direct measurement of global and regional metabolic wall thickening with 18F-FDG-gated positron emission tomography (PET) in patients with coronary artery disease (CAD). Based on non-invasive (ECG, echocardiography) and invasive [cineventriculography (CVG), coronary angiography] investigations, 12 patients with CAD underwent gated metabolic PET studies with 18F-FDG. Myocardial wall thickening and wall motion analysis from short-axis horizontal and vertical long-axis slices were studied. PET-derived global ejection fraction correlated with CVG-derived global ejection fraction (r = 0.75). Forty-eight of 72 segments investigated were normal (66.7%); 24 of 72 segments were abnormal (33.3%), of which 10 (41.7%) were considered to be hibernating. Four segments were classified as partially fibrotic (16.7%) and 10 (41.7%) as entirely scar-like. Gated PET (8 gates, tail drop corrected) allows quantification of global and regional ejection fraction to detect metabolic wall thickening in left ventricular segments with dyskinesia on CVG due to critical CAD stenoses. By improving data analysis methods, our approach may enhance the detection of viable, hibernating myocardium before revascularization.

Combined arthroscopic and radiation synovectomy in rheumatoid arthritis.

In rheumatoid arthritis of the knee joint good results are obtained using arthroscopic synovectomy or radiation synovectomy. Aim of our study was to investigate, wether the combination of these two minimal invasive interventions achieves better results. First we performed arthroscopic synovectomy of the knee joint followed by radiation synovectomy with application of 111-222 MBq Yttrium-90 6 weeks later. In a prospective randomised clinical trial between 1987 and 1991 we performed radiation synovectomy on 22 knee joints and combined arthroscopic and radiation synovectomy on 26 knee joints. We explored the patients preoperatively, 6 weeks and 6 months postoperatively. In 1996 we evaluated 141 knee joints in a retrospective clinical trial. 90 Knee joints had been treated with the combined therapy, 39 only with radiation synovectomy and 12 only with arthroscopic synovectomy. Depending on the three different therapeutic interventions, the patients were classified into mid-term (3-5 years) and long-term (6-8 years) observation groups. The trials are based on the standardized ARO-Questionnaire of the knee joint, the modified ARO Knee-Score and the radiological grading according to Larsen, Dale and Eek. In the prospective clinical trial we found significant better results for patients treated with the combined therapy than for patients treated with radiation synovectomy only regarding the parameter swelling, effusion, range of motion, pain and Knee-Score. In the long-term results of the retrospective clinical trial the patients treated with the combined therapy showed a significant better outcome for the parameters pain, swelling and Knee-Score, than the patients treated with radiation synovectomy. Although no statistically significant difference was found comparing the results of the combined therapy with arthroscopic synovectomy, an improvement of the clinical outcome can be observed performing arthroscopic synovectomy followed by radiation synovectomy. In the treatment of rheumatoid arthritis of the knee joint a better outcome is achieved performing combined arthroscopic and radiation synovectomy than performing only one of the methods.