Malignant melanoma is the most aggressive cancer of the skin. The 5-year survival is 99% for loca... more Malignant melanoma is the most aggressive cancer of the skin. The 5-year survival is 99% for localized disease but drops off rapidly to 65% for patients with regional metastases, and declines further to 15% for patients with distant metastases at the time of diagnosis [3]. This dramatic reduction in survival of patients with disseminated disease requires the accurate identification of metastases at the time of initial diagnosis and during follow-up. This chapter reviews the role of positron emission tomography (PET) and combined positron emission tomography with computed tomography (PET/CT) in the management of patients with malignant melanoma.
Accurate staging of non-small cell lung cancer (NSCLC) is essential for subsequent treatment. Thi... more Accurate staging of non-small cell lung cancer (NSCLC) is essential for subsequent treatment. This study was designed to evaluate the value of FDG-PET in detecting unexpected extrathoracic metastases (ETM) in patients with NSCLC qualifying for surgical treatment based on conventional staging. One hundred patients with stage IIIa or less were included and underwent clinical evaluation, chest and upper abdominal CT scan, mediastinoscopy, and routine laboratory tests. If clinical signs of EM were present additional diagnostic methods, were applied. A partial body FDG-PET was performed. All findings in the FDG-PET were confirmed histologically or radiologically. Unknown ETM were detected in 13 patients (14%) at 19 sites. Whole-body FDG-PET improves detection of unsuspected ETM in patients with NSCLC otherwise eligible for surgery. Fourteen percent of patients were understaged.
Using the very well investigated and sensitive microsomal monooxynogenase aryl hydrocarbon hydrol... more Using the very well investigated and sensitive microsomal monooxynogenase aryl hydrocarbon hydrolase (AHH), we investigated the dose-response relations between an inducer, 3-methylcholanthrene (3-MC), and an inhibitor of transcription, actinomycin D (ACT D), in 10 days old rats. An optimum pretreatment schedule proved to be a single dose of 1 to 40 mg/kg 3-MC ip combined with two administrations of 200 to 600 microgram/kg ACT D within 16 hr. With increasing doses of ACT D the inhibition of 3-MC-mediated AHH induction increased up to 88%. With 7,8-benzoflavone (ANF) as a relatively specific in vitro inhibitor of the cytochrome P-448 species no distinct influence on the constitutive AHH activity could be observed up to the 30th days of age. In 60 and 200 days old rats the inhibition reached a significant level of about 50%. After 3-MC induction a nearly uniform ANF-mediated inhibition by about 50% of the hepactic AHH activity was observed: in older animals the percentage became slight...
Methods in molecular biology (Clifton, N.J.), 2011
Accurate staging is essential to offer the patient the most effective available treatment and the... more Accurate staging is essential to offer the patient the most effective available treatment and the best estimate of prognosis. In non-small cell lung cancer (NSCLC), surgical resection offers the best chance of cure in the early stages, either alone or in combination with chemo- or radiotherapy at the more advanced stages. However, many patients present with metastatic disease at the time of diagnosis. Both computed tomography (CT) and positron emission tomography (PET) using fluorodeoxyglucose (FDG) play an important role in the diagnosis and staging of lung cancer. CT provides excellent morphologic information but has significant limitations in differentiating between benign and malignant lesions either in an organ or in lymph nodes. FDG-PET is highly accurate in the detection of mediastinal lymph node metastases as well as extratharacic metastases. However, due to the poor anatomic information provided by PET, additional morphologic information is needed to properly locate a lesio...
Langenbecks Archiv für Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft für Chirurgie. Kongress, 1998
Accurate staging of non-small cell lung cancer (NSCLC) is essential for subsequent treatment. Thi... more Accurate staging of non-small cell lung cancer (NSCLC) is essential for subsequent treatment. This study was designed to evaluate the value of FDG-PET in detecting unexpected extrathoracic metastases (ETM) in patients with NSCLC qualifying for surgical treatment based on conventional staging. One hundred patients with stage IIIa or less were included and underwent clinical evaluation, chest and upper abdominal CT scan, mediastinoscopy, and routine laboratory tests. If clinical signs of EM were present additional diagnostic methods, were applied. A partial body FDG-PET was performed. All findings in the FDG-PET were confirmed histologically or radiologically. Unknown ETM were detected in 13 patients (14%) at 19 sites. Whole-body FDG-PET improves detection of unsuspected ETM in patients with NSCLC otherwise eligible for surgery. Fourteen percent of patients were understaged.
To prospectively determine the accuracy of positron emission tomography (PET)/computed tomography... more To prospectively determine the accuracy of positron emission tomography (PET)/computed tomography (CT) with added CT morphologic information for depiction of metastases in patients with high-risk melanoma and negative findings for metastases at PET, by using histologic findings or additional imaging and/or follow-up findings as reference standard. Institutional review board approval was obtained. Informed consent was obtained from patients. One hundred twenty-four consecutive high-risk melanoma patients (65 female, 59 male; mean age, 54.4 years; range, 15-82 years) were included. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT was performed. First, PET/CT scans were evaluated for presence of metastases with increased FDG uptake; CT anatomic location was determined. Lesions were considered metastases if there was focal uptake higher than that of background tissue. Second, coregistered CT images of combined PET/CT scans were evaluated for presence of lesions without FDG uptake. Findings were compared with reference standard findings to determine the accuracy of each evaluation. McNemar test was used to assess statistical differences in accuracy. In 53 of 124 patients, metastases were found. In 46 of 53 patients with metastases, lesions had increased FDG uptake. In seven patients with metastatic disease, metastases did not have increased FDG uptake (maximum standard uptake value [SUV], <1.5; n = 5) or had faint FDG uptake (maximum SUV, 2.5 and 2.9; n = 2)-findings that were inconclusive with PET alone. These lesions were interpreted as metastases only with coregistered CT images. Lesions missed with PET were located in the lungs, iliac lymph nodes, subcutis, and psoas muscle. Sensitivity, specificity, and accuracy, respectively, of PET/CT for depiction of metastases were 85%, 96%, and 91%, and those of PET/CT with dedicated CT interpretation were 98%, 94%, and 96% (P = .016). Dedicated analysis of coregistered CT images significantly improves the accuracy of integrated PET/CT for depiction of metastases in patients with high-risk melanoma.
The aim of this study was to compare prospectively the accuracy of whole-body positron emission t... more The aim of this study was to compare prospectively the accuracy of whole-body positron emission tomography (PET), CT and MRI in diagnosing primary and recurrent ovarian cancer. Nineteen patients (age range 23-76 years) were recruited with suspicious ovarian lesions at presentation (n = 8) or follow-up for recurrence (n = 11). All patients were scheduled for laparotomy and histological confirmation. Whole-body PET with FDG, contrast-enhanced spiral CT of the abdomen, including the pelvis, and MRI of the entire abdomen were performed. Each imaging study was evaluated separately. Imaging findings were correlated with histopathological diagnosis. The sensitivity, specificity and accuracy for lesion characterization in patients with suspicious ovarian lesions (n = 7) were, respectively: 100, 67 and 86% for PET; 100, 67 and 86% for CT; and 100, 100 and 100% for MRI. For the diagnosis of recurrent disease (n = 10), PET had a sensitivity of 100%, specificity of 50% and accuracy of 90%. The PET technique was the only technique which correctly identified a single transverse colon metastasis. Results for CT were 40, 50 and 43%, and for MRI 86, 100 and 89%, respectively. No statistically significant difference was seen. Neither FDG PET nor CT nor MRI can replace surgery in the detection of microscopic peritoneal disease. No statistically significant difference was observed for the investigated imaging modalities with regard to lesion characterization or detection of recurrent disease; thus, the methods are permissible alternatives. The PET technique, however, has the drawback of less accurate spatial assignment of small lesions compared with CT and MRI.
Cardiovascular risk factors in Prader-Willi syndrome (PWS, OMIM 176270) may be independently caus... more Cardiovascular risk factors in Prader-Willi syndrome (PWS, OMIM 176270) may be independently caused by overweight or hypothalamic growth hormone (GH) de®ciency. The present observational study in 23 children with PWS, aged 0.3±14.6 years, focuses on the speci®c pattern, age-dependency and interrelation of cardiovascular risk factors, namely percentage fat mass and regional fat distribution, triglycerides (TG), lipoprotein cholesterols (LDL-C, HDL-C), lipoprotein (a) (Lp(a)), apolipoproteins A-I (Apo A-I) and B (Apo B), as well as on the longer-term eects of GH therapy (ca. 0.037 mg/kg per day for 3 years on average). We report that in children above 4 years, percentage body fat was increased in all and waist-to-hip-ratio (WHR) in 35%. Abnormal levels of LDL-C, Apo B, HDL-C and TG were found in 6, 7, 6 and 3 children, respectively. Lp(a) was above 300 mg/l in 5 patients and remained unchanged during GH therapy. However, percentage fat mass dropped to the upper normal range and WHR became normal in all patients receiving GH therapy, as did the ratio of LDL-C to HDL-C, subsequent to decreasing LDL-C and increasing HDL-C. Nevertheless, we could not ®nd any signi®cant correlation between parameters of total fat mass or fat distribution and serum lipid parameters, except for abdominal fat distribution (trunk-/leg-fat ratio) to TG before therapy. Conclusion Several cardiovascular risk factors are already present in prepubertal children with Prader-Willi-syndrome and they are improved by growth hormone treatment, acting both on body composition and lipid metabolism.
Bone loss and osteoporotic fractures are common in cardiac transplant recipients. To compare two ... more Bone loss and osteoporotic fractures are common in cardiac transplant recipients. To compare two prophylactic medical regimens after heart transplantation, 26 consecutive heart transplant recipients were randomized to receive either continuous oral calcitriol (0.5 g/day) combined with nasal salmon calcitonin (200 U/day) for the first 3 months (group A) or intermittent intravenous pamidronate (0.5 mg/kg body weight) every third month (group B). Bone mineral density (BMD) and biochemical indices of bone turnover were measured at baseline and 3, 6, 12, and 18 months after transplantation. The mean pretransplant BMD, measured by dual energy X-ray absorptiometry (DXA) was significantly lower in the patients compared with agematched healthy controls. During the first year of treatment, rates of bone loss at the lumbar spine and femoral neck were slightly but significantly slower in the patients treated with pamidronate, but there was no longer a significant difference between the two groups after 18 months of heart transplantation. Irrespective of the mode of osteoporosis prevention, osteocalcin levels increased whereas urinary deoxypyridinoline decreased after transplantation, and significant bone loss was observed in both treatment groups. We found no relationship between initial BMD, markers of bone turnover, cumulative glucocorticoid dose, or cyclosporine levels and the rate of bone loss after cardiac transplantation. In summary, we found that the rapid and severe bone loss following heart transplantation could be attenuated by two preventive measures, pamidronate or calcitriol with calcitonin.
Tyrosine is a precursor of melanin synthesis and might thus present a valuable marker for melanom... more Tyrosine is a precursor of melanin synthesis and might thus present a valuable marker for melanoma. The aim of this study was to evaluate the uptake of alpha-methyl-tyrosine (AMT) in melanoma cell cultures and to assess its usefulness as a radiopharmaceutical for staging melanoma patients with whole-body scintigraphy. Melanoma (M19-cell lines) and fibroblast (negative control) cell cultures were incubated with 125I-AMT and the radioactive uptake in the cell lines was measured in a gamma-counter over 24 h. For in vivo studies, planar whole-body scintigraphy and single photon emission computed tomography (SPECT) of the tumour region was performed following injection of 250-350 MBq 123I-AMT in six patients with known melanoma metastases. Findings were compared with results of whole-body positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) as a standard of reference. Fibroblasts showed an unchanged uptake of (mean +/- SD) 0.56 +/- 0.09% 15 min and 0.066 +/- 0.09% 24 h, respectively, after incubation of 125I-AMT, whereas there was an increased uptake in melanoma cell cultures over time from 0.9 +/- 0.05% to 7.5 +/- 1.6%. In staging melanoma patients, the sensitivity of whole-body AMT-scintigraphy compared with FDG-PET was 37% (10 of 27 metastases). AMT is transported and metabolized to a high extent in melanoma cells and 123I-AMT is accumulated in melanoma metastases. Owing to its low sensitivity, however, the clinical use of whole-body AMT scintigraphy cannot be recommended.
Accurate staging of non-small cell lung cancer is essential for treatment planning. We evaluated ... more Accurate staging of non-small cell lung cancer is essential for treatment planning. We evaluated in a prospective study the role of whole-body 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in mediastinal nodal staging with a positive predictive value of 96%. The study was continued to further evaluate the value of whole-body FDG PET in detecting unexpected extrathoracic metastases (ETMs) in patients qualifying for surgical treatment by conventional staging. One hundred patients underwent clinical evaluation, chest and upper abdominal computed tomography scan, mediastinoscopy (lymph nodes greater than 1 cm on computed tomography), and routine laboratory tests. In 94 patients with stage IIIa or less and 6 with suspected N3 a whole-body FDG PET was performed. If clinical signs of ETMs were present additional diagnostic methods were applied. All findings in the FDG PET were confirmed histologically or radiologically. Unexpected ETMs were detected in 13 (14%) of 94 patients (stage IIIa or less) at 14 sites. In addition 6 of 94 patients were restaged up to N3 after PET. The suspected N3 disease (stage IIIb) on computed tomography was confirmed by PET in all 6 patients. There was no false positive finding of ETM. Weight loss was correlated with the occurrence of ETM: more than 5 kg, 5 of 13 patients (38%); more than 10 kg, 4 of 6 patients (67%). Pathologic laboratory findings were not predictive for ETM. Whole-body FDG PET improves detection of ETMs in patients with non-small cell lung cancer otherwise elegible for operation. In 14% of patients (stage IIIa or less), ETMs were detected, and in total, 20% of the patients were understaged.
1. Acad Radiol. 1998 Sep;5 Suppl 2:S300-2. Cost-effectiveness of whole-body PET imaging in non-sm... more 1. Acad Radiol. 1998 Sep;5 Suppl 2:S300-2. Cost-effectiveness of whole-body PET imaging in non-small cell lung cancer and malignant melanoma. von Schulthess GK, Steinert HC, Dummer R, Weder W. Department of Medical ...
International Journal of Radiation Oncology*Biology*Physics, 2003
To investigate the usefulness of hardware coregistered PET/CT images for target volume definition... more To investigate the usefulness of hardware coregistered PET/CT images for target volume definition. Thirty-nine patients presenting with various solid tumors were investigated. CT and a FDG-PET were obtained in treatment position in an integrated PET/CT scanner, and coregistered images were used for treatment planning. First, volume delineation was performed on the CT data. In a second step, the corresponding PET data were used as an overlay to the CT data to define the target volume. Delineation was done independently by two investigators. Coregistered PET/CT showed good fusion accuracy. The GTV increased by 25% or more because of PET in 17% of cases with head-and-neck (2/12) and lung cancer (1/6), and in 33% (7/21) in cancer of the pelvis. The GTV was reduced > or =25% in 33% of patients with head-and-neck cancer (4/12), in 67% with lung cancer (4/6), and 19% with cancer of the pelvis (4/21). Overall, in 56% (22/39) of cases, GTV delineation was changed significantly if information from metabolic imaging was used in the planning process. The modification of the GTV translated into altered PTV changes exceeding >20% in 46% (18/39) of cases. With PET, volume delineation variability between two independent oncologists decreased from a mean volume difference of 25.7 cm(3) to 9.2 cm(3) associated with a reduction of the standard deviation from 38.3 cm(3) to 13.3 cm(3) (p = 0.02). In 16% of cases, PET/CT revealed distant metastasies, changing the treatment strategy from curative to palliative. Integrated PET/CT for treatment planning for three-dimensional conformal radiation therapy improves the standardization of volume delineation compared with that of CT alone. PET/CT has the potential for reducing the risk for geographic misses, to minimize the dose of ionizing radiation applied to non-target organs, and to change the current practice to three-dimensional conformal radiation therapy planning by taking into account the metabolic and biologic features of cancer. The impact on treatment outcome remains to be demonstrated.
Malignant melanoma is the most aggressive cancer of the skin. The 5-year survival is 99% for loca... more Malignant melanoma is the most aggressive cancer of the skin. The 5-year survival is 99% for localized disease but drops off rapidly to 65% for patients with regional metastases, and declines further to 15% for patients with distant metastases at the time of diagnosis [3]. This dramatic reduction in survival of patients with disseminated disease requires the accurate identification of metastases at the time of initial diagnosis and during follow-up. This chapter reviews the role of positron emission tomography (PET) and combined positron emission tomography with computed tomography (PET/CT) in the management of patients with malignant melanoma.
Accurate staging of non-small cell lung cancer (NSCLC) is essential for subsequent treatment. Thi... more Accurate staging of non-small cell lung cancer (NSCLC) is essential for subsequent treatment. This study was designed to evaluate the value of FDG-PET in detecting unexpected extrathoracic metastases (ETM) in patients with NSCLC qualifying for surgical treatment based on conventional staging. One hundred patients with stage IIIa or less were included and underwent clinical evaluation, chest and upper abdominal CT scan, mediastinoscopy, and routine laboratory tests. If clinical signs of EM were present additional diagnostic methods, were applied. A partial body FDG-PET was performed. All findings in the FDG-PET were confirmed histologically or radiologically. Unknown ETM were detected in 13 patients (14%) at 19 sites. Whole-body FDG-PET improves detection of unsuspected ETM in patients with NSCLC otherwise eligible for surgery. Fourteen percent of patients were understaged.
Using the very well investigated and sensitive microsomal monooxynogenase aryl hydrocarbon hydrol... more Using the very well investigated and sensitive microsomal monooxynogenase aryl hydrocarbon hydrolase (AHH), we investigated the dose-response relations between an inducer, 3-methylcholanthrene (3-MC), and an inhibitor of transcription, actinomycin D (ACT D), in 10 days old rats. An optimum pretreatment schedule proved to be a single dose of 1 to 40 mg/kg 3-MC ip combined with two administrations of 200 to 600 microgram/kg ACT D within 16 hr. With increasing doses of ACT D the inhibition of 3-MC-mediated AHH induction increased up to 88%. With 7,8-benzoflavone (ANF) as a relatively specific in vitro inhibitor of the cytochrome P-448 species no distinct influence on the constitutive AHH activity could be observed up to the 30th days of age. In 60 and 200 days old rats the inhibition reached a significant level of about 50%. After 3-MC induction a nearly uniform ANF-mediated inhibition by about 50% of the hepactic AHH activity was observed: in older animals the percentage became slight...
Methods in molecular biology (Clifton, N.J.), 2011
Accurate staging is essential to offer the patient the most effective available treatment and the... more Accurate staging is essential to offer the patient the most effective available treatment and the best estimate of prognosis. In non-small cell lung cancer (NSCLC), surgical resection offers the best chance of cure in the early stages, either alone or in combination with chemo- or radiotherapy at the more advanced stages. However, many patients present with metastatic disease at the time of diagnosis. Both computed tomography (CT) and positron emission tomography (PET) using fluorodeoxyglucose (FDG) play an important role in the diagnosis and staging of lung cancer. CT provides excellent morphologic information but has significant limitations in differentiating between benign and malignant lesions either in an organ or in lymph nodes. FDG-PET is highly accurate in the detection of mediastinal lymph node metastases as well as extratharacic metastases. However, due to the poor anatomic information provided by PET, additional morphologic information is needed to properly locate a lesio...
Langenbecks Archiv für Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft für Chirurgie. Kongress, 1998
Accurate staging of non-small cell lung cancer (NSCLC) is essential for subsequent treatment. Thi... more Accurate staging of non-small cell lung cancer (NSCLC) is essential for subsequent treatment. This study was designed to evaluate the value of FDG-PET in detecting unexpected extrathoracic metastases (ETM) in patients with NSCLC qualifying for surgical treatment based on conventional staging. One hundred patients with stage IIIa or less were included and underwent clinical evaluation, chest and upper abdominal CT scan, mediastinoscopy, and routine laboratory tests. If clinical signs of EM were present additional diagnostic methods, were applied. A partial body FDG-PET was performed. All findings in the FDG-PET were confirmed histologically or radiologically. Unknown ETM were detected in 13 patients (14%) at 19 sites. Whole-body FDG-PET improves detection of unsuspected ETM in patients with NSCLC otherwise eligible for surgery. Fourteen percent of patients were understaged.
To prospectively determine the accuracy of positron emission tomography (PET)/computed tomography... more To prospectively determine the accuracy of positron emission tomography (PET)/computed tomography (CT) with added CT morphologic information for depiction of metastases in patients with high-risk melanoma and negative findings for metastases at PET, by using histologic findings or additional imaging and/or follow-up findings as reference standard. Institutional review board approval was obtained. Informed consent was obtained from patients. One hundred twenty-four consecutive high-risk melanoma patients (65 female, 59 male; mean age, 54.4 years; range, 15-82 years) were included. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT was performed. First, PET/CT scans were evaluated for presence of metastases with increased FDG uptake; CT anatomic location was determined. Lesions were considered metastases if there was focal uptake higher than that of background tissue. Second, coregistered CT images of combined PET/CT scans were evaluated for presence of lesions without FDG uptake. Findings were compared with reference standard findings to determine the accuracy of each evaluation. McNemar test was used to assess statistical differences in accuracy. In 53 of 124 patients, metastases were found. In 46 of 53 patients with metastases, lesions had increased FDG uptake. In seven patients with metastatic disease, metastases did not have increased FDG uptake (maximum standard uptake value [SUV], <1.5; n = 5) or had faint FDG uptake (maximum SUV, 2.5 and 2.9; n = 2)-findings that were inconclusive with PET alone. These lesions were interpreted as metastases only with coregistered CT images. Lesions missed with PET were located in the lungs, iliac lymph nodes, subcutis, and psoas muscle. Sensitivity, specificity, and accuracy, respectively, of PET/CT for depiction of metastases were 85%, 96%, and 91%, and those of PET/CT with dedicated CT interpretation were 98%, 94%, and 96% (P = .016). Dedicated analysis of coregistered CT images significantly improves the accuracy of integrated PET/CT for depiction of metastases in patients with high-risk melanoma.
The aim of this study was to compare prospectively the accuracy of whole-body positron emission t... more The aim of this study was to compare prospectively the accuracy of whole-body positron emission tomography (PET), CT and MRI in diagnosing primary and recurrent ovarian cancer. Nineteen patients (age range 23-76 years) were recruited with suspicious ovarian lesions at presentation (n = 8) or follow-up for recurrence (n = 11). All patients were scheduled for laparotomy and histological confirmation. Whole-body PET with FDG, contrast-enhanced spiral CT of the abdomen, including the pelvis, and MRI of the entire abdomen were performed. Each imaging study was evaluated separately. Imaging findings were correlated with histopathological diagnosis. The sensitivity, specificity and accuracy for lesion characterization in patients with suspicious ovarian lesions (n = 7) were, respectively: 100, 67 and 86% for PET; 100, 67 and 86% for CT; and 100, 100 and 100% for MRI. For the diagnosis of recurrent disease (n = 10), PET had a sensitivity of 100%, specificity of 50% and accuracy of 90%. The PET technique was the only technique which correctly identified a single transverse colon metastasis. Results for CT were 40, 50 and 43%, and for MRI 86, 100 and 89%, respectively. No statistically significant difference was seen. Neither FDG PET nor CT nor MRI can replace surgery in the detection of microscopic peritoneal disease. No statistically significant difference was observed for the investigated imaging modalities with regard to lesion characterization or detection of recurrent disease; thus, the methods are permissible alternatives. The PET technique, however, has the drawback of less accurate spatial assignment of small lesions compared with CT and MRI.
Cardiovascular risk factors in Prader-Willi syndrome (PWS, OMIM 176270) may be independently caus... more Cardiovascular risk factors in Prader-Willi syndrome (PWS, OMIM 176270) may be independently caused by overweight or hypothalamic growth hormone (GH) de®ciency. The present observational study in 23 children with PWS, aged 0.3±14.6 years, focuses on the speci®c pattern, age-dependency and interrelation of cardiovascular risk factors, namely percentage fat mass and regional fat distribution, triglycerides (TG), lipoprotein cholesterols (LDL-C, HDL-C), lipoprotein (a) (Lp(a)), apolipoproteins A-I (Apo A-I) and B (Apo B), as well as on the longer-term eects of GH therapy (ca. 0.037 mg/kg per day for 3 years on average). We report that in children above 4 years, percentage body fat was increased in all and waist-to-hip-ratio (WHR) in 35%. Abnormal levels of LDL-C, Apo B, HDL-C and TG were found in 6, 7, 6 and 3 children, respectively. Lp(a) was above 300 mg/l in 5 patients and remained unchanged during GH therapy. However, percentage fat mass dropped to the upper normal range and WHR became normal in all patients receiving GH therapy, as did the ratio of LDL-C to HDL-C, subsequent to decreasing LDL-C and increasing HDL-C. Nevertheless, we could not ®nd any signi®cant correlation between parameters of total fat mass or fat distribution and serum lipid parameters, except for abdominal fat distribution (trunk-/leg-fat ratio) to TG before therapy. Conclusion Several cardiovascular risk factors are already present in prepubertal children with Prader-Willi-syndrome and they are improved by growth hormone treatment, acting both on body composition and lipid metabolism.
Bone loss and osteoporotic fractures are common in cardiac transplant recipients. To compare two ... more Bone loss and osteoporotic fractures are common in cardiac transplant recipients. To compare two prophylactic medical regimens after heart transplantation, 26 consecutive heart transplant recipients were randomized to receive either continuous oral calcitriol (0.5 g/day) combined with nasal salmon calcitonin (200 U/day) for the first 3 months (group A) or intermittent intravenous pamidronate (0.5 mg/kg body weight) every third month (group B). Bone mineral density (BMD) and biochemical indices of bone turnover were measured at baseline and 3, 6, 12, and 18 months after transplantation. The mean pretransplant BMD, measured by dual energy X-ray absorptiometry (DXA) was significantly lower in the patients compared with agematched healthy controls. During the first year of treatment, rates of bone loss at the lumbar spine and femoral neck were slightly but significantly slower in the patients treated with pamidronate, but there was no longer a significant difference between the two groups after 18 months of heart transplantation. Irrespective of the mode of osteoporosis prevention, osteocalcin levels increased whereas urinary deoxypyridinoline decreased after transplantation, and significant bone loss was observed in both treatment groups. We found no relationship between initial BMD, markers of bone turnover, cumulative glucocorticoid dose, or cyclosporine levels and the rate of bone loss after cardiac transplantation. In summary, we found that the rapid and severe bone loss following heart transplantation could be attenuated by two preventive measures, pamidronate or calcitriol with calcitonin.
Tyrosine is a precursor of melanin synthesis and might thus present a valuable marker for melanom... more Tyrosine is a precursor of melanin synthesis and might thus present a valuable marker for melanoma. The aim of this study was to evaluate the uptake of alpha-methyl-tyrosine (AMT) in melanoma cell cultures and to assess its usefulness as a radiopharmaceutical for staging melanoma patients with whole-body scintigraphy. Melanoma (M19-cell lines) and fibroblast (negative control) cell cultures were incubated with 125I-AMT and the radioactive uptake in the cell lines was measured in a gamma-counter over 24 h. For in vivo studies, planar whole-body scintigraphy and single photon emission computed tomography (SPECT) of the tumour region was performed following injection of 250-350 MBq 123I-AMT in six patients with known melanoma metastases. Findings were compared with results of whole-body positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) as a standard of reference. Fibroblasts showed an unchanged uptake of (mean +/- SD) 0.56 +/- 0.09% 15 min and 0.066 +/- 0.09% 24 h, respectively, after incubation of 125I-AMT, whereas there was an increased uptake in melanoma cell cultures over time from 0.9 +/- 0.05% to 7.5 +/- 1.6%. In staging melanoma patients, the sensitivity of whole-body AMT-scintigraphy compared with FDG-PET was 37% (10 of 27 metastases). AMT is transported and metabolized to a high extent in melanoma cells and 123I-AMT is accumulated in melanoma metastases. Owing to its low sensitivity, however, the clinical use of whole-body AMT scintigraphy cannot be recommended.
Accurate staging of non-small cell lung cancer is essential for treatment planning. We evaluated ... more Accurate staging of non-small cell lung cancer is essential for treatment planning. We evaluated in a prospective study the role of whole-body 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in mediastinal nodal staging with a positive predictive value of 96%. The study was continued to further evaluate the value of whole-body FDG PET in detecting unexpected extrathoracic metastases (ETMs) in patients qualifying for surgical treatment by conventional staging. One hundred patients underwent clinical evaluation, chest and upper abdominal computed tomography scan, mediastinoscopy (lymph nodes greater than 1 cm on computed tomography), and routine laboratory tests. In 94 patients with stage IIIa or less and 6 with suspected N3 a whole-body FDG PET was performed. If clinical signs of ETMs were present additional diagnostic methods were applied. All findings in the FDG PET were confirmed histologically or radiologically. Unexpected ETMs were detected in 13 (14%) of 94 patients (stage IIIa or less) at 14 sites. In addition 6 of 94 patients were restaged up to N3 after PET. The suspected N3 disease (stage IIIb) on computed tomography was confirmed by PET in all 6 patients. There was no false positive finding of ETM. Weight loss was correlated with the occurrence of ETM: more than 5 kg, 5 of 13 patients (38%); more than 10 kg, 4 of 6 patients (67%). Pathologic laboratory findings were not predictive for ETM. Whole-body FDG PET improves detection of ETMs in patients with non-small cell lung cancer otherwise elegible for operation. In 14% of patients (stage IIIa or less), ETMs were detected, and in total, 20% of the patients were understaged.
1. Acad Radiol. 1998 Sep;5 Suppl 2:S300-2. Cost-effectiveness of whole-body PET imaging in non-sm... more 1. Acad Radiol. 1998 Sep;5 Suppl 2:S300-2. Cost-effectiveness of whole-body PET imaging in non-small cell lung cancer and malignant melanoma. von Schulthess GK, Steinert HC, Dummer R, Weder W. Department of Medical ...
International Journal of Radiation Oncology*Biology*Physics, 2003
To investigate the usefulness of hardware coregistered PET/CT images for target volume definition... more To investigate the usefulness of hardware coregistered PET/CT images for target volume definition. Thirty-nine patients presenting with various solid tumors were investigated. CT and a FDG-PET were obtained in treatment position in an integrated PET/CT scanner, and coregistered images were used for treatment planning. First, volume delineation was performed on the CT data. In a second step, the corresponding PET data were used as an overlay to the CT data to define the target volume. Delineation was done independently by two investigators. Coregistered PET/CT showed good fusion accuracy. The GTV increased by 25% or more because of PET in 17% of cases with head-and-neck (2/12) and lung cancer (1/6), and in 33% (7/21) in cancer of the pelvis. The GTV was reduced > or =25% in 33% of patients with head-and-neck cancer (4/12), in 67% with lung cancer (4/6), and 19% with cancer of the pelvis (4/21). Overall, in 56% (22/39) of cases, GTV delineation was changed significantly if information from metabolic imaging was used in the planning process. The modification of the GTV translated into altered PTV changes exceeding >20% in 46% (18/39) of cases. With PET, volume delineation variability between two independent oncologists decreased from a mean volume difference of 25.7 cm(3) to 9.2 cm(3) associated with a reduction of the standard deviation from 38.3 cm(3) to 13.3 cm(3) (p = 0.02). In 16% of cases, PET/CT revealed distant metastasies, changing the treatment strategy from curative to palliative. Integrated PET/CT for treatment planning for three-dimensional conformal radiation therapy improves the standardization of volume delineation compared with that of CT alone. PET/CT has the potential for reducing the risk for geographic misses, to minimize the dose of ionizing radiation applied to non-target organs, and to change the current practice to three-dimensional conformal radiation therapy planning by taking into account the metabolic and biologic features of cancer. The impact on treatment outcome remains to be demonstrated.
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Papers by Hans Steinert