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ABSTRACT: Ipilimumab is a human monoclonal antibody directed against a receptor expressed on activated T-lymphocytes (CTLA-4). Binding to this receptor induces T-cell activation against tumor cells. A 77-year-old man with a stage IV metastatic melanoma was treated with ipilimumab. F-FDG PET-CT performed for response evaluation revealed intense uptake in the pituitary gland. Two weeks later, biochemical parameters altered confirming hypophysitis. Treatment of the hypophysitis was started, and shortly thereafter, biochemical parameters normalized. Follow-up PET-CT revealed normalization of F-FDG uptake in the pituitary gland. In this case, we present a patient with ipilimumab-induced hypophysitis initially diagnosed on F-FDG PET-CT.
Clinical nuclear medicine 04/2013; 38(4):e182-4. · 3.92 Impact Factor
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ABSTRACT: Neurolymphomatosis is defined as infiltration of the nervous system by hematological malignancy and is difficult to diagnose. We report a case of a 57-year-old man, treated for small B-cell non-Hodgkin lymphoma, presenting with sensorimotor impairment of the lower limbs, which started 6 years after diagnosis. He was treated with chemotherapy, after which, the symptoms disappeared. After 7 months, he developed sensorimotor impairment of both upper limbs. MRI of the brachial plexus showed no abnormalities. F-FDG PET-CT showed increased uptake at the brachial plexus and nerves, suggesting neurolymphomatosis. Confirmatory biopsy revealed conversion of the malignancy to diffuse large B-cell lymphoma.
Clinical nuclear medicine 09/2012; · 3.92 Impact Factor
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ABSTRACT: The aim of this study was to systematically review literature, exploring the role of radioguided surgery with iodine-labeled metaiodobenzylguanidine (MIBG) in resection of neuroendocrine tumors.
PubMed, EMBASE, Web of Science, COCHRANE, CINAHL, Academic Search Premier, ScienceDirect, Wiley, and references of key articles were searched to identify potentially relevant studies.
Twenty studies were included. A total of 130 procedures in 120 patients were performed. Ninety percent of included studies concerned case reports or case series. It is described that radioguided surgery with iodine-labeled MIBG can improve the quality of macroscopic resection of neuroendocrine tumors in selected cases, ie, in cases where the tumor is small, nonpalpable, difficult to visualize on conventional imaging studies, or located in an area with adhesional scar tissue from previous surgery. However, in a substantial number of cases the gamma probe failed due to technical problems.
Since there is limited evidence that radioguided surgery contributes substantially in resection of neuroendocrine tumors, we cannot advocate its use in general. However, we can conclude that it can seemingly improve the quality of resection in selected cases. When radioguided surgery is performed in neuroendocrine tumors, we advocate the use of I to label MIBG.
Clinical nuclear medicine 09/2012; 37(11):1083-8. · 3.92 Impact Factor
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ABSTRACT: Radioactive MIBG can be used in radioguided surgery for neuroendocrine tumors. We report the case of a man with a mutation in the succinate dehydrogenase subunit B (SDHB) gene, in which an abdominal MRI scan identified two 5-mm left para-aortic nodules, suspect for paragangliomas. Subsequent SPECT revealed increased uptake of tracer. 123I MIBG probe-guided resection was scheduled. During surgery, 2 small nodules with elevated activity in between the superior mesenteric artery and the left adrenal gland were identified by the detection probe and were resected. Histopathologic examination revealed mature ganglioneuromas.
Clinical nuclear medicine 08/2012; 37(8):768-71. · 3.92 Impact Factor
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ABSTRACT: Neurolymphomatosis (NL) is a rare clinical entity that is defined as infiltration of the nervous system by a known or unknown haematological malignancy and is difficult to diagnose. Fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging is increasingly being used in haematological malignancies. This article focus on the role of 18F-FDG PET in the diagnosis and management of NL by presenting a review of cases described in the literature. Reports on NL that used PET with or without computed tomography (CT) as a diagnostic modality were extracted from Medline and evaluated. A total of 58 patients described in 49 case reports on NL were found. In 36 distinctive patients 18F-FDG PET with or without CT was used as a diagnostic modality. In 91% of patients PET showed uptake in various structures in the central or peripheral nervous system, suggesting involvement of lymphoma. Predilection localizations were the brachial and lumbar plexuses, along the course of peripheral nerves of the extremities, and the trigeminal nerve root. MRI, cerebrospinal fluid or bone marrow analysis were frequently negative. In the cases described in the literature 18F-FDG PET assisted in diagnosing NL by providing a whole-body evaluation, showing frequent uptake in affected nervous structures and supported disease management by defining a target for biopsy, monitoring progression and evaluating response to treatment. As other diagnostic methods may be negative, the importance of PET-CT is increasing in the diagnosis and management of this rare clinical entity.
Nuclear Medicine Communications 06/2012; 33(9):907-16. · 1.40 Impact Factor
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European Journal of Nuclear Medicine 01/2012; 39(5):919-20. · 4.53 Impact Factor
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ABSTRACT: Fluorine-18-methyl-choline (F18-choline) PET/computed tomography (CT) is routinely performed in our hospital for patients with significantly increased or rapidly increasing prostate-specific antigen (PSA) levels to detect and localize recurrent prostate carcinoma. We observed uptake of this PET tracer in mediastinal lymph nodes in a significant number of patients. The aim of this study was to assess the frequency of this finding and to determine whether it is correlated with tumour and nontumour-related aspects.
A total of 48 consecutive men (mean age: 65.6 years; range: 50-79 years, standard deviation: 7.1) with histopathologically proven prostate cancer were referred for F18-choline PET/CT imaging for restaging from March 2009 to October 2010. All patients had a suspicion of tumour recurrence because of an increased PSA or a rapidly increasing PSA. All studies were reviewed, and the results were correlated with general data such as age; smoking; chronic obstructive pulmonary disease; tumor, lymph nodes and distant metastases stage; Gleason Score and PSA level; with a maximum interval of 3 months between serum PSA and the PET/CT scan.
In 27 patients (56.3%), F18-choline PET/CT showed positive lymph nodes in the mediastinum (mean standardized uptake values: 3.75; range: 1.7-13.8, standard deviation: 2.4). No histological biopsy was carried out in F18-choline-positive lymph nodes, but in none of the patients was mediastinal recurrence or pulmonary infection observed during a 6-month follow-up. Only one patient had histologically proven pulmonary metastasis. No significant relationship was observed between mediastinal F18-choline lymph node uptake and serum PSA level (P=0.785), initial T stage (P=0.555), N stage (P=0.548), M stage (P=0.426), smoking (P=0.537), chronic obstructive pulmonary disease (P=0.115) or the presence of tumour recurrence on F18-choline PET/CT.
Mediastinal lymph node uptake of F18 choline is frequently observed, without any significant relationship with tumour characteristics. Therefore, interpretation of positive mediastinal lymph node uptake should be done carefully.
Nuclear Medicine Communications 12/2011; 32(12):1143-7. · 1.40 Impact Factor
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Cornelis J Roos,
Roxana Djaberi,
Joanne D Schuijf,
Eelco J de Koning,
Ton J Rabelink,
Jan W Smit,
Alberto M Pereira,
Imad Al Younis, Bernies van der Hiel,
Arthur J Scholte,
Jeroen J Bax,
J Wouter Jukema
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ABSTRACT: Vascular stiffness may potentially be used as a screening tool to identify asymptomatic patients with diabetes with abnormal myocardial perfusion. The purpose of this study was therefore to determine the association between vascular stiffness, measured in term of pulse wave velocity (PWV) and augmentation index (AIx), and abnormal myocardial perfusion imaging (MPI) in asymptomatic patients with diabetes.
Prospectively, 160 asymptomatic patients with diabetes (mean age 51 years, 87 men) underwent MPI with adenosine stress. The summed stress score (SSS) was determined in each patient according to a 17-segment and five-point score. Abnormal MPI (SSS ≥ 3) was classified as moderate (SSS 3-7) or severe (SSS ≥ 8) MPI defects. Using applanation tonometry, the carotid-femoral PWV and the radial AIx corrected to 75 beats per minute were determined noninvasively.
MPI was abnormal in 61 patients (38%), with severe MPI defects in 22 patients (14%). Mean PWV increased with deteriorating MPI from 8.4 ± 2.2 m/s in normal MPI to 9.0 ± 2.2 m/s in moderate MPI defects (p = 0.11) and to 11.1 ± 2.5 m/s in severe MPI defects (p < 0.01). Likewise, mean AIx increased from 18.4 ± 13.4% to 19.4 ± 10.7% (p = 0.66) and to 25.4 ± 9.0% (p = 0.03). After adjustment for age and other risk factors, PWV remained a significant predictor of severe MPI defects (p = 0.01, OR 1.50, 95% CI 1.11-2.00), whereas AIx was no longer significant (p = 0.20).
Vascular stiffness measured by PWV is associated with severe MPI defects in asymptomatic patients with diabetes.
European Journal of Nuclear Medicine 08/2011; 38(11):2050-7. · 4.53 Impact Factor
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Mark J Boogers,
Ji Chen,
Caroline E Veltman,
Rutger J van Bommel,
Eline A Q Mooyaart,
Imad Al Younis, Bernies van der Hiel,
Petra Dibbets-Schneider,
Ernst E van der Wall,
Martin J Schalij,
Ernest V Garcia,
Jeroen J Bax,
Victoria Delgado
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ABSTRACT: The aim of the current study was to evaluate the feasibility of phase analysis on gated myocardial perfusion SPECT (GMPS) for the assessment of left ventricular (LV) diastolic dyssynchrony in a head-to-head comparison with tissue Doppler imaging (TDI).
The population consisted of patients with end-stage heart failure of New York Heart Association functional class III or IV with a reduced LV ejection fraction of ≤ 35%. LV diastolic dyssynchrony was calculated using TDI as the maximal time delay between early peak diastolic velocities of two opposing left ventricle walls (diastolic mechanical delay). Significant LV diastolic dyssynchrony was defined as a diastolic mechanical delay of >55 ms on TDI. Furthermore, phase analysis on GMPS was performed to evaluate LV diastolic dyssynchrony; diastolic phase standard deviation (SD) and histogram bandwidth (HBW) were used as markers of LV diastolic dyssynchrony.
A total of 150 patients (114 men, mean age 66.0 ± 10.4 years) with end-stage heart failure were enrolled. Both diastolic phase SD (r = 0.81, p < 0.01) and diastolic HBW (r = 0.75, p < 0.01) showed good correlations with LV diastolic dyssynchrony on TDI. Additionally, patients with LV diastolic dyssynchrony on TDI (>55 ms) showed significantly larger diastolic phase SD (68.1 ± 13.4° vs. 40.7 ± 14.0°, p < 0.01) and diastolic HBW (230.6 ± 54.3° vs. 129.0 ± 55.6°, p < 0.01) as compared to patients without LV diastolic dyssynchrony on TDI (≤ 55 ms). Finally, phase analysis on GMPS showed a good intra- and interobserver reproducibility for the determination of diastolic phase SD (ICC 0.97 and 0.88) and diastolic HBW (ICC 0.98 and 0.93).
Phase analysis on GMPS showed good correlations with TDI for the assessment of LV diastolic dyssynchrony.
European Journal of Nuclear Medicine 08/2011; 38(11):2031-9. · 4.53 Impact Factor
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Razvan L Miclea,
Marcel Karperien,
Alexandra M Langers,
Els C Robanus-Maandag,
Antoon van Lierop, Bernies van der Hiel,
Marcel P Stokkel,
Bart E Ballieux,
Wilma Oostdijk,
Jan M Wit,
Hans F Vasen,
Neveen A Hamdy
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ABSTRACT: The canonical Wnt pathway plays a key regulatory role in osteoblastogenesis and bone mass acquisition through its main effector, β-catenin. Adenomatous polyposis coli (APC) represents the key intracellular gatekeeper of β-catenin turnover, and heterozygous germ-line mutations in the APC gene cause familial adenomatous polyposis (FAP). Whether APC mutations affect bone mass has not been previously investigated. We conducted a cross-sectional study evaluating skeletal status in FAP patients with a documented APC mutation. Twenty-two FAP patients with a mean age of 42 years (54.5% women) were included in this study. Mean bone mineral density (BMD) Z-scores were significantly increased above normal at all measured sites: lumbar spine (p < .01), total hip (p < .01), femoral neck (p < .05), and trochanter (p < .01). Z-scores were +1 or greater in 14 patients (63.6%) and +2 or greater in 5 (22.7%). Mean values of bone turnover markers were within normal ranges. There was a significant positive correlation between procollagen type I N-terminal propeptide (P1NP) and β-crosslaps (β-CTX) (r = 0.70, p < .001) and between these markers and sclerostin and BMD measurements. We demonstrate that FAP patients display a significantly higher than normal mean BMD compared with age- and sex-matched healthy controls in the presence of a balanced bone turnover. Our data suggest a state of "controlled" activation of the Wnt signaling pathway in heterozygous carriers of APC mutations, most likely owing to upregulation of cytoplasmic β-catenin levels.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 12/2010; 25(12):2624-32. · 6.04 Impact Factor
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Mark J Boogers,
Ji Chen,
Rutger J van Bommel,
C Jan Willem Borleffs,
Petra Dibbets-Schneider, Bernies van der Hiel,
Imad Al Younis,
Martin J Schalij,
Ernst E van der Wall,
Ernest V Garcia,
Jeroen J Bax
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ABSTRACT: The aim of the current study was to evaluate the relationship between the site of latest mechanical activation as assessed with gated myocardial perfusion SPECT (GMPS), left ventricular (LV) lead position and response to cardiac resynchronization therapy (CRT).
The patient population consisted of consecutive patients with advanced heart failure in whom CRT was currently indicated. Before implantation, 2-D echocardiography and GMPS were performed. The echocardiography was performed to assess LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). The site of latest mechanical activation was assessed by phase analysis of GMPS studies and related to LV lead position on fluoroscopy. Echocardiography was repeated after 6 months of CRT. CRT response was defined as a decrease of ≥15% in LVESV.
Enrolled in the study were 90 patients (72% men, 67±10 years) with advanced heart failure. In 52 patients (58%), the LV lead was positioned at the site of latest mechanical activation (concordant), and in 38 patients (42%) the LV lead was positioned outside the site of latest mechanical activation (discordant). CRT response was significantly more often documented in patients with a concordant LV lead position than in patients with a discordant LV lead position (79% vs. 26%, p<0.01). After 6 months, patients with a concordant LV lead position showed significant improvement in LVEF, LVESV and LVEDV (p<0.05), whereas patients with a discordant LV lead position showed no significant improvement in these variables.
Patients with a concordant LV lead position showed significant improvement in LV volumes and LV systolic function, whereas patients with a discordant LV lead position showed no significant improvements.
European Journal of Nuclear Medicine 10/2010; 38(2):230-8. · 4.53 Impact Factor
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ABSTRACT: ST-segment depression during adenosine stress testing is usually a 1-time event during or after the test and is often related to ischemia due to severe 3-vessel disease. In this case report we describe a patient with severe 3-vessel disease who had intermittent ST-segment depression on the electrocardiogram during a myocardial perfusion stress test with adenosine. These intermittent ST depressions could be explained by possible adenosine-induced coronary spasm.
Clinical Nuclear Medicine 01/2008; 32(12):927-9. · 3.67 Impact Factor
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ABSTRACT: To evaluate therapy with high doses of (111)Indium pentetreotide in a patient with bone metastases from a carcinoid of the pancreas.
A 55-Year-old male presented in November 1990 with stomach ache with dorsal irradiation. Ultrasonography and computed tomography (CT-) scans of the abdomen revealed a tumour of the tail of the pancreas and liver metastases. Histological examination revealed a neuroendocrine tumour. Surgery and polychemotherapy were initiated and after seven cycles a tumour regression of 30% was achieved. During follow-up multiple metastases were seen upon bone scintigraphy for which treatment with high doses Indium-111-octreotide was initiated.
The patient underwent eight cycles, with one cycle every 5 weeks. Each treatment consisted of an i.v. injection of 6 GBq Indium-111-pentetreotide. Comparing the results of the first and the last post-treatment scintigraphy, a regression of the number and intensity of uptake in the lesions was found. Bone scintigraphy showed a regression of the skeletal lesions as well, while X-ray, CT-scan and chromogranin-A levels showed stable disease.
Results from the treatment of our patient indicate that the use of high dose radiolabelled somatostatin analogues could be of significant use, even in the case of bone metastases. To our knowledge, this is the first report describing therapeutic effects on bone metastases from a neuroendocrine tumour.
European Journal of Endocrinology 01/2004; 149(6):479-83. · 3.42 Impact Factor
