[Show abstract][Hide abstract] ABSTRACT: We reviewed reoperations for persistent or recurrent sporadic parathyroid adenoma to evaluate and compare our current results and outcomes to our previous experience.
From 1996 to 2008, 237 patients with persistent or recurrent hyperparathyroidism after failed operation underwent reoperation. Patients were re-explored with the assistance of non-invasive and sometimes invasive imaging.
A missed adenoma was suspected pre-operatively in 163 patients. Reoperation resulted in long-term resolution of hypercalcemia in 92%. Adenomas were in entopic locations in 32%; the most frequent ectopic location was the thymus (20%). Sestamibi scanning and ultrasonography were the most successful non-invasive imaging studies (96% positive predictive value (PPV) and 84% PPV respectively). Forty-four percent of patients had a reoperation based solely on non-invasive imaging. Of the invasive procedures performed, arteriography resulted in the best localization (92% PPV). Permanent recurrent laryngeal nerve injury occurred in 1.8%.
Compared to our prior experience (1982-1995), outcomes remained similar (92% resolution of hypercalcemia and 1.8% recurrent nerve injury currently versus 96% and 1.3% previously). Fewer patients received invasive studies for pre-operative localization (56% vs 73%, respectively). The decreased use of invasive imaging is due to technical improvements and greater confidence in the combination of ultrasonography and sestamibi scanning.
Surgery 12/2009; 146(6):1144-55. DOI:10.1016/j.surg.2009.09.015 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Besides (123)I-metaiodobenzylguanidine (MIBG), positron emission tomography (PET) agents are available for the localization of paraganglioma (PGL), including (18)F-3,4-dihydroxyphenylalanine (DOPA), (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), and (18)F-fluorodopamine ((18)F-FDA).
The objective of the study was to establish the optimal approach to the functional imaging of PGL and examine the link between genotype-specific tumor biology and imaging.
This was a prospective observational study.
There were no interventions.
Fifty-two patients (28 males, 24 females, aged 46.8 +/- 14.2 yr): 20 with nonmetastatic PGL (11 adrenal), 28 with metastatic PGL (13 adrenal), and four in whom PGL was ruled out; 22 PGLs were of the succinate dehydrogenase subunit B (SDHB) genotype.
Sensitivity of (18)F-DOPA, (18)F-FDG, and (18)F-FDA PET, (123)I-MIBG scintigraphy, computed tomography (CT), and magnetic resonance imaging (MRI) for the localization of PGL were measured.
Sensitivities for localizing nonmetastatic PGL were 100% for CT and/or MRI, 81% for (18)F-DOPA PET, 88% for (18)F-FDG PET/CT, 78% for (18)F-FDA PET/CT, and 78% for (123)I-MIBG scintigraphy. For metastatic PGL, sensitivity in reference to CT/MRI was 45% for (18)F-DOPA PET, 74% for (18)F-FDG PET/CT, 76% for (18)F-FDA PET/CT, and 57% for (123)I-MIBG scintigraphy. In patients with SDHB metastatic PGL, (18)F-FDA and (18)F-FDG have a higher sensitivity (82 and 83%) than (123)I-MIBG (57%) and (18)F-DOPA (20%).
(18)F-FDA PET/CT is the preferred technique for the localization of the primary PGL and to rule out metastases. Second best, equal alternatives are (18)F-DOPA PET and (123)I-MIBG scintigraphy. For patients with known metastatic PGL, we recommend (18)F-FDA PET in patients with an unknown genotype, (18)F-FDG or (18)F-FDA PET in SDHB mutation carriers, and (18)F-DOPA or (18)F-FDA PET in non-SDHB patients.
The Journal of Clinical Endocrinology and Metabolism 10/2009; 94(12):4757-67. DOI:10.1210/jc.2009-1248 · 6.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Imaging modalities available for the localization of phaeochromocytoma (PHEO) include computed tomography (CT), magnetic resonance imaging (MRI), [(123)I]- or [(131)I]-labelled metaiodobenzylguanidine ((123/131)I-MIBG) scintigraphy and 6-[(18)F]-fluorodopamine ((18)F-FDA) positron emission tomography (PET). Our aim was to investigate the yield of (18)F-FDA PET vs. biochemical testing and other imaging techniques to establish the diagnosis and location of PHEO.
The study included 99 consecutive patients (35 Males, 64 Females, mean +/- SD age 46.4 +/- 13.4 years), who underwent (18)F-FDA PET, biochemical testing (plasma catecholamines and free metanephrines) and CT and/or MRI. The majority (78%) also underwent (123/131)I-MIBG.
In total 26 patients had non-metastatic PHEO, 34 patients had metastatic PHEO, and PHEO was ruled out in 39 patients. Investigations to rule out or confirm PHEO yielded the following sensitivity/specificity: plasma metanephrines 97/95%, (18)F-FDA 92/90%, (123)I-MIBG 83/100%, (123/131)I-MIBG 70/100%, CT 100/41%, MRI 98/60%. Sensitivities for localizing non-metastatic PHEO on a per-lesion base were: CT 97%, MRI 92%, (18)F-FDA 78%, (123)I-MIBG 78% and (123/131)I-MIBG 76%. Sensitivities for detecting metastases on a per-patient base were: CT and MRI 100%, (18)F-FDA 97%, (123)I-MIBG 85% and (123/131)I-MIBG 65%.
For tumour localization, (18)F-FDA PET and (123/131)I-MIBG scintigraphy perform equally well in patients with non-metastatic PHEO, but metastases are better detected by (18)F-FDA PET than by (123/131)I-MIBG.
[Show abstract][Hide abstract] ABSTRACT: ONJ is an important toxicity in cancer patients receiving bisphosphonate therapy. Here we report a higher than usual incidence of ONJ, 11 of 60 (18.3%, 95% Confidence Interval, CI: 9%-28%) patients enrolled in a phase II clinical trial combining bevacizumab, docetaxel, thalidomide, and prednisone (ATTP) in chemotherapy-naive men with metastatic castration resistant prostate cancer (mCRPC). The use of bisphosphonates was allowed at study entry. Our study suggests that anti-angiogenic and chemotherapy agents can predispose to the development of ONJ in men with mCRPC on zoledronic acid. Imaging modalities, such as bone scans, may be useful in following the clinical course of patients who develop ONJ.
Cancer Investigation 03/2009; 27(2):221-6. DOI:10.1080/07357900802208608 · 2.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine if sorafenib is associated with an improved 4-month probability of progression-free survival, using radiographic and clinical criteria alone, in patients with metastatic castration-resistant prostate cancer. Secondary endpoints included pharmacokinetics, toxicity analysis and overall survival.
The study was an open-label, phase II, two-stage design, focusing on the results from the second stage, as criteria for progression were modified after completing the first stage. Sorafenib was given at a dose of 400 mg orally twice daily in 28-day cycles. Clinical and laboratory assessments were done every 4 weeks, and radiographic scans were obtained every 8 weeks.
Twenty-four patients were accrued in the second stage; the median (range) age was 66 (49-85) years, the on-study prostate-specific antigen level was 68.45 (5.8-995) ng/mL, the Gleason score 8 (6-9) and Eastern Cooperative Oncology Group status 1 (in 17 patients). Of the 24 patients, 21 had previous chemotherapy with docetaxel. All patients had bony metastases, either alone (in 11) or with soft-tissue disease (in 13). One patient had a partial response; 10 patients had stable disease (median duration 18 weeks, range 15-48). At a median potential follow-up of 27.2 months, the median progression-free survival was 3.7 months and the median overall survival was 18.0 months. For the whole trial of 46 patients the median survival was 18.3 months. Most frequent toxicities included hand-foot skin reaction (grade 2 in nine patients, grade 3 in three), rash, abnormalities in liver function tests, and fatigue.
Sorafenib has moderate activity as a second-line treatment for metastatic castration-resistant prostate cancer.
BJU International 02/2009; 103(12):1636-40. DOI:10.1111/j.1464-410X.2008.08327.x · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared functional imaging modalities including PET with 6-(18)F-fluorodopamine ((18)F-DA) with (123)I-metaiodobenzylguanidine ((123)I-MIBG) and somatostatin receptor scintigraphy (SRS) with (111)In-pentetreotide in nonmetastatic and metastatic pheochromocytoma (PHEO).
We studied 25 men and 28 women (mean age +/- SD, 44.2 +/- 14.2 y) with biochemically proven nonmetastatic (n = 17) or metastatic (n = 36) PHEO. Evaluation included anatomic imaging with CT or MRI and functional imaging that included at least 2 nuclear medicine modalities: (18)F-DA PET, (123)I-MIBG scintigraphy, or SRS. Sensitivity of functional imaging versus anatomic imaging was assessed on a per-patient and a per-region basis.
For this available cohort, on a per-patient basis overall sensitivity (combined for nonmetastatic and metastatic PHEO) was 90.2% for (18)F-DA PET, 76.0% for (123)I-MIBG scintigraphy, and 22.0% for SRS. On a per-region basis, overall sensitivity was 75.4% for (18)F-DA PET, 63.4% for (123)I-MIBG scintigraphy, and 64.0% for SRS.
If available, (18)F-DA PET should be used in the evaluation of PHEO, because it is more sensitive than (123)I-MIBG scintigraphy or SRS. If (18)F-DA PET is not available, (123)I-MIBG scintigraphy (for nonmetastatic or adrenal PHEO) and SRS (for metastatic PHEO) should be the first alternative imaging methods to be used.
Journal of Nuclear Medicine 10/2008; 49(10):1613-9. DOI:10.2967/jnumed.108.052373 · 6.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We performed a retrospective analysis of 71 subjects with metastatic pheochromocytoma and paraganglioma (30 subjects with mutation of succinate dehydrogenase enzyme subunit B (SDHB) gene and 41 subjects without SDHB mutation). Sixty-nine percent presented with bone metastases (SDHB +/-: 77% vs 63%), 39% with liver metastases (SDHB +/-: 27% vs 47%), and 32% with lung metastases (SDHB +/-: 37% vs 29%). The most common sites of bone involvement were thoracic spine (80%; SDHB+/-: 83% vs 77%), lumbar spine (78%; SDHB +/-: 78% vs 75%), and pelvic and sacral bones (78%; SDHB +/-: 91% vs 65%, P=0.04). Subjects with SDHB mutation also showed significantly higher involvement of long bones (SDHB +/-: 78% vs 30%, P=0.007) than those without the mutation. The best overall sensitivity in detecting bone metastases demonstrated positron emission tomography (PET) with 6-[(18)F]-fluorodopamine ([(18)F]-FDA; 90%), followed by bone scintigraphy (82%), computed tomography or magnetic resonance imaging (CT/MRI; 78%), 2-[(18)F]-fluoro-2-deoxy-d-glucose ([(18)F]-FDG) PET (76%), and scintigraphy with [(123/131)I]-metaiodobenzylguanidine (71%). In subjects with SDHB mutation, imaging modalities with best sensitivities for detecting bone metastases were CT/MRI (96%), bone scintigraphy (95%), and [(18)F]-FDG PET (92%). In subjects without SDHB mutations, the modality with the best sensitivity for bone metastases was [(18)F]-FDA PET (100%). In conclusion, bone scintigraphy should be used in the staging of patients with malignant pheochromocytoma and paraganglioma, particularly in patients with SDHB mutations. As for PET imaging, [(18)F]-FDG PET is highly recommended in SDHB mutation patients, whereas [(18)F]-FDA PET is recommended in patients without the mutation.
Endocrine Related Cancer 04/2008; 15(1):311-23. DOI:10.1677/ERC-07-0217 · 4.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To prospectively evaluate the outcome of patients with acute deep vein thrombosis (DVT) of the lower extremity treated with "lacing" of the thrombus with alteplase (recombinant tissue plasminogen activator, or rTPA).
This HIPAA-compliant study was approved by the Institutional Review Board of the National Heart, Lung, and Blood Institute and was funded by the National Institutes of Health. After giving written consent, 20 patients with first-onset acute DVT were treated with direct intraclot lacing of the thrombus with alteplase (maximum daily dose, 50 mg per leg per day; maximum of four treatments) and full systemic anticoagulation. Alteplase was chosen because its high fibrin affinity obviates continuous infusion of this thrombolytic agent. Ventilation-perfusion (V/Q) scans were performed for evaluation of embolic risks, and clinical and imaging examinations were supplemented with pharmacokinetic studies to enable further assessment of treatment outcomes.
The 20 patients included 13 men and seven women aged 18-79 years. Antegrade blood flow was restored throughout the deep venous system in 16 patients (80%) during thrombolytic therapy, with complete resolution of symptoms in 18 patients (90%) after 6 months of anticoagulation. Pharmacokinetic studies showed rapid clearance of circulating alteplase and recovery of plasminogen activator inhibitor-1 levels within 2 hours after termination of alteplase treatment. V/Q scans revealed a 40% incidence of pulmonary embolism before treatment and a 15% incidence of asymptomatic pulmonary embolism during thrombolytic therapy. There were no cases of clinically important pulmonary embolism or serious bleeding during thrombolytic therapy. During a mean follow-up period of 3.4 years, no patient developed a postthrombotic syndrome or recurrent thromboembolism.
Intraclot injection or lacing of the thrombus with a fibrin-binding thrombolytic agent such as alteplase is an alternative to continuous-infusion thrombolytic regimens and minimizes the duration of systemic exposure to thrombolytic agents.
[Show abstract][Hide abstract] ABSTRACT: To determine if sorafenib is associated with a 4-month probability of progression-free survival, which is consistent with 50%, as determined by clinical, radiographic, and prostate-specific antigen (PSA) criteria in patients with metastatic androgen-independent prostate cancer (AIPC).
Patients with progressive metastatic AIPC were enrolled in an open-label, single-arm phase II study. Sorafenib was given continuously at a dose of 400 mg orally twice daily in 28-day cycles. Clinical assessment and PSA measurement were done every cycle whereas radiographic measurements were carried out every two cycles.
Twenty-two patients were enrolled in the study to date, completing a planned first stage of the trial. Baseline patient characteristics included a median age of 63.9 years (range, 50-77 years), Gleason score of 9 (range, 4-9.5), and PSA concentration of 53.3 ng/mL (range, 2-1,905 ng/mL). Fifty-nine percent of patients had received one prior chemotherapy regimen. Of the 21 patients with progressive disease, 13 progressed only by PSA criteria in the absence of evidence of clinical and radiographic progression. Two patients were found to have dramatic reduction of bone metastatic lesions as shown by bone scan, although they met PSA progression criteria at the time when scans were obtained. Toxicities likely related to treatment included one grade 3 hypertension; one grade 3 hand-foot syndrome; and grade 1/2 toxicities: fatigue, anorexia, hypertension, skin rash, nausea, and diarrhea. Results from in vitro studies suggested that PSA is not a good marker of sorafenib activity. The geometric mean exposure (AUC(0-12)) and maximum concentration (C(max)) were 9.76 h mg/L and 1.28 mg/L, respectively. The time to maximum concentration (t(max)) and accumulation ratio (after second dose) ranged from 2 to 12 h and 0.68 to 6.43, respectively.
Sorafenib is relatively well tolerated in AIPC with two patients showing evidence of improved bony metastatic lesions. Interpretation of this study is complicated by discordant radiographic and PSA responses. PSA may not be an adequate biomarker for monitoring sorafenib activity. Based on these observations, further investigation using only clinical and radiographic end points as progression criteria is warranted. Accrual to the second stage of trial is ongoing.
Clinical Cancer Research 02/2008; 14(1):209-14. DOI:10.1158/1078-0432.CCR-07-1355 · 8.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 6-(18)F-Fluorodopamine ((18)F-FDA) PET is a highly sensitive tool for the localization of pheochromocytoma (PHEO). The aim of this study was to establish cutoff values for pathologic and physiologic adrenal gland tracer uptake.
(18)F-FDA PET with CT coregistration was performed in 14 patients (10 men and 4 women; age [mean +/- SD], 42.9 +/- 13.3 y) with unilateral adrenal gland PHEO and in 13 control subjects (5 men and 8 women; age, 51.7 +/- 12.5 y) without PHEO. Standardized uptake values (SUVs) were compared between adrenal glands with PHEO and normal left adrenal glands in control subjects.
(18)F-FDA accumulation was observed in all adrenal glands with PHEO and in 6 of 13 control adrenal glands (P = 0.02). The SUV was higher in adrenal glands with PHEO (mean +/- SD, 16.1 +/- 6.1) than in (18)F-FDA-positive control adrenal glands (7.7 +/- 1.4) (P = 0.005). SUV cutoffs for distinguishing between adrenal glands with PHEO and normal adrenal glands were 7.3 (100% sensitivity) and 10.1 (100% specificity).
The SUVs of adrenal foci on (18)F-FDA PET facilitate the distinction between adrenal glands with PHEO and normal adrenal glands.
Journal of Nuclear Medicine 01/2008; 48(12):1940-4. DOI:10.2967/jnumed.107.043281 · 6.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 6-(18)F-fluoro-l-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET is a useful tool for the detection of certain neuroendocrine tumors, especially with the preadministration of carbidopa, an inhibitor of DOPA decarboxylase. Whether carbidopa also improves (18)F-DOPA PET of adrenal pheochromocytomas and extraadrenal paragangliomas is unknown. The aim of this study was to investigate the sensitivity of (18)F-DOPA PET in the detection of paraganglioma and its metastatic lesions and to evaluate whether tracer uptake by the tumors is enhanced by carbidopa.
Two patients with nonmetastatic adrenal pheochromocytoma, and 9 patients with extraadrenal abdominal paraganglioma (1 nonmetastatic, 8 metastatic), underwent whole-body CT, MRI, baseline (18)F-DOPA PET, and (18)F-DOPA PET with oral preadministration of 200 mg of carbidopa. The dynamics of tracer uptake by these lesions and the physiologic distribution of (18)F-DOPA in normal tissues were recorded.
Seventy-eight lesions were detected by CT or MRI, 54 by baseline (18)F-DOPA PET (P = 0.0022 vs. CT/MRI), and 57 by (18)F-DOPA PET plus carbidopa (P = 0.0075 vs. CT/MRI, not statistically significant vs. baseline). In reference to findings on CT and MRI, the sensitivities of baseline (18)F-DOPA PET were 47.4% for lesions and 55.6% for positive body regions, versus 50.0% (lesions) and 66.7% (regions) for (18)F-DOPA PET plus carbidopa (neither is statistically significant vs. baseline). Compared with baseline, carbidopa detected additional lesions in 3 (27%) of 11 patients. Carbidopa increased the mean (+/-SD) peak standardized uptake value in index tumor lesions from 6.4 +/- 3.9 to 9.1 +/- 5.6 (P = 0.037). Pancreatic physiologic (18)F-DOPA uptake, which may mask adrenal pheochromocytoma, is blocked by carbidopa.
Carbidopa enhances the sensitivity of (18)F-DOPA PET for adrenal pheochromocytomas and extraadrenal abdominal paragangliomas by increasing the tumor-to-background ratio of tracer uptake. The sensitivity of (18)F-DOPA PET for metastases of paraganglioma appears to be limited.
Journal of Nuclear Medicine 11/2007; 48(10):1599-606. DOI:10.2967/jnumed.107.042721 · 6.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy.
Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder in which normal bone is replaced by abnormal fibro-osseous tissue. Variable amounts of skeletal involvement and disability occur. The age at which lesions are established, the pace at which the disease progresses, if (or when) the disease plateaus, and how these parameters relate to the onset of disability are unknown. To answer these questions, we performed a retrospective analysis of a group of subjects with FD.
One hundred nine subjects with a spectrum of FD were studied for up to 32 years. Disease progression was assessed in serial (99)Tc-MDP bone scans by determining the location and extent of FD lesions using a validated bone scan scoring tool. Physical function and the need for ambulatory aids were assessed.
Ninety percent of the total body disease skeletal burden was established by age 15. Disease was established in a region-specific pattern; in the craniofacial region, 90% of the lesions were present by 3.4 yr, in the extremities, 90% were present by 13.7 yr, and in the axial skeleton, 90% were present by 15.5 yr. Twenty-five of 103 subjects eventually needed ambulatory aids. The median age at which assistance was needed was 7 yr (range, 1-43 yr). The median bone scan score for subjects needing assistance was 64.3 (range, 18.6-75) compared with 23.1 (range, 0.5-63.5) in the unassisted subjects (p < 0.0001). Among subjects needing assistance with ambulation, 92% showed this need by 17 yr.
The majority of skeletal lesions and the associated functional disability occur within the first decade of life. The implication is that the window of time for preventative therapies is narrow. Likewise, therapeutic interventions must be tailored to where the patient is in the natural history of the disease (i.e., progressive disease [young] versus established disease [older subjects]). These findings have implications for prognosis, the timing and type of therapy, and the development of trials of new therapies and their interpretation.
Journal of Bone and Mineral Research 09/2007; 22(9):1468-74. DOI:10.1359/jbmr.070511 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several radiopharmaceuticals such as (18)F-FDG, (123)I-metaiodobenzylguanidine (MIBG), and (99m)Tc-tetrofosmin have demonstrated uptake in brown adipose tissue (BAT). It is important to recognize these normal variants so that they are not misinterpreted as a significant pathologic state. In addition, these radiopharmaceuticals may shed light on BAT physiology. (18)F-6-fluorodopamine (F-DA) is being used as a PET radiopharmaceutical to image adrenergic innervation and suspected pheochromocytoma. Past reports have suggested that BAT is increased in pheochromocytoma patients.
The images of 96 patients evaluated with (18)F-F-DA or (18)F-FDG PET/CT for known or suspected pheochromocytoma were reviewed retrospectively to determine whether localized uptake of a pattern typically associated with BAT was present. When available, contemporaneous images obtained using (123)I-MIBG were also reviewed for the presence of BAT.
Of 67 patients imaged with (18)F-F-DA, BAT was found in 17.9%. Of 83 patients imaged with (18)F-FDG, 19.2% had BAT. Discordant findings related to uptake in BAT were often seen in patients studied with (18)F-FDG, (18)F-F-DA, or (123)I-MIBG. Overall, 26 (27.0%) of 96 patients showed BAT on at least 1 of the 3 imaging modalities.
(18)F-F-DA can image BAT, most likely by localizing to sympathetic innervations in a manner similar to (123)I-MIBG. Patients with pheochromocytoma may have a greater BAT tissue mass or activation because of elevated levels of circulating catecholamines. Quantitative PET with (18)F-FDG and (18)F-F-DA may have a role in in vivo studies of BAT physiology in humans or animal models.
Journal of Nuclear Medicine 08/2007; 48(7):1077-83. DOI:10.2967/jnumed.106.035915 · 6.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Germline mutations of the gene encoding subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) predispose to malignant paraganglioma (PGL). Timely and accurate localization of these aggressive tumors is critical for guiding optimal treatment. Our aim is to evaluate the performance of functional imaging modalities in the detection of metastatic lesions of SDHB-associated PGL.
Sensitivities for the detection of metastases were compared between [18F]fluorodopamine ([18F]FDA) and [18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), iodine-123- (123I) and iodine-131 (131I) -metaiodobenzylguanidine (MIBG), 111In-pentetreotide, and Tc-99m-methylene diphosphonate bone scintigraphy in 30 patients with SDHB-associated PGL. Computed tomography (CT) and magnetic resonance imaging (MRI) served as standards of reference.
Twenty-nine of 30 patients had metastatic lesions. In two patients, obvious metastatic lesions on functional imaging were missed by CT and MRI. Sensitivity according to patient/body region was 80%/65% for 123I-MIBG and 88%/70% for [18F]FDA-PET. False-negative results on 123I-MIBG scintigraphy and/or [18F]FDA-PET were not predicted by genotype or biochemical phenotype. [18F]FDG-PET yielded a by patient/by body region sensitivity of 100%/97%. At least 90% of regions that were false negative on 123I-MIBG scintigraphy or [18F]FDA-PET were detected by [18F]FDG-PET. In two patients, 111In-pentetreotide scintigraphy detected liver lesions that were negative on other functional imaging modalities. Sensitivities were similar before and after chemotherapy or 131I-MIBG treatment, except for a trend toward lower post- (60%/41%) versus pretreatment (80%/65%) sensitivity of 123I-MIBG scintigraphy.
With a sensitivity approaching 100%, [18F]FDG-PET is the preferred functional imaging modality for staging and treatment monitoring of SDHB-related metastatic PGL.
[Show abstract][Hide abstract] ABSTRACT: Although pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) associated with high mortality, there exist few data characterizing hemodynamics and cardiopulmonary function in this population.
To characterize hemodynamics and cardiopulmonary function in patients with SCD with and without PH.
Patients with SCD with PH (n = 26) were compared with control subjects with SCD but without PH (n = 17), matched for age, hemoglobin levels, and fetal hemoglobin levels.
Upon catheterization, 54% of the patients with PH had pulmonary arterial hypertension, and 46% had pulmonary venous hypertension. When compared with control subjects, patients with PH exhibited lower six-minute-walk distance (435 +/- 31 vs. 320 +/- 20 m, p = 0.002) and oxygen consumption (50 +/- 3% vs. 41 +/- 2% of predicted, p = 0.02), and also had mild restrictive lung disease and more perfusion abnormalities on radionuclide lung scans. The six-minute-walk distance in this population inversely correlated with tricuspid regurgitant jet velocity (r = -0.55, p < 0.001), and mean pulmonary artery pressure (r = -0.57, p < 0.001), and directly correlated with maximal oxygen consumption (r = 0.49, p = 0.004), even after adjustment for hemoglobin, supporting an independent contribution of increasing pulmonary artery pressures to loss of exercise capacity.
Patients with SCD-associated PH have both pulmonary arterial and venous PH associated with severe limitations in exercise capacity, likely compounded by interstitial lung fibrosis and severe anemia. These data support the use of the six-minute-walk distance as an index of PH and cardiopulmonary function in patients with SCD.
American Journal of Respiratory and Critical Care Medicine 07/2007; 175(12):1272-9. DOI:10.1164/rccm.200610-1498OC · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: [(123/131)I]metaiodobenzylguanidine (MIBG) scintigraphy is considered as the gold standard in the localization of pheochromocytoma. However, this method has less optimal sensitivity for the detection of pheochromocytoma associated with von Hippel-Lindau (VHL). Our preliminary results suggest that this is partially due to the low expression of cell membrane norepinephrine transporter system in VHL-related pheochromocytoma cells. Another probable cause may be the low affinity that [(123/131)I]MIBG has for these cells. Recently, 6-[(18)F]fluorodopamine ([(18)F]DA) positron emission tomography (PET) has been introduced as a novel functional imaging modality with high sensitivity for pheochromocytoma. Therefore, we investigated whether [(18)F]DA PET is more effective than [(123/131)I]MIBG scintigraphy in the diagnostic localization of VHL-related adrenal pheochromocytoma.
In this study, we evaluated seven VHL patients in whom adrenal pheochromocytomas were confirmed by histopathology results. Adrenal pheochromocytomas were localized using computed tomography (CT), magnetic resonance imaging (MRI), [(123/131)I]MIBG scintigraphy and [(18)F]DA PET.
[(18)F]DA PET localized pheochromocytoma in all the seven patients, as did in CT. In contrast, three out of the seven had negative results utilizing [(123/131)I]MIBG scintigraphy and one out of the six patients had negative MRI results.
[(18)F]DA PET was found to show more promising results when compared with [(123/131)I]MIBG scintigraphy in the diagnostic localization of VHL-related adrenal pheochromocytoma, with a 100% rate of localization. Thus, [(18)F]DA PET in conjunction with CT/MRI should be considered as an effective method for the proper localization of VHL-related adrenal pheochromocytoma.
European Journal of Endocrinology 05/2007; 156(4):483-7. DOI:10.1530/EJE-06-0712 · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify patients with androgen-independent prostate cancer (AIPC) with bone metastasis and no soft-tissue metastases at the time of protocol enrollment, and analyse their disease progression by computed tomography (CT), bone scan, and prostate-specific antigen (PSA) level to determine the utility of routine interval CT in such patients.
Bone is the most common metastatic site in patients with AIPC and the only site of metastatic disease for many; because some with initial bone metastasis eventually develop soft-tissue disease, many clinical trials use routine CT to monitor for the latter as a sign of disease progression, but the actual incidence of new soft-tissue metastases is unknown and the role of routine interval CT in monitoring for disease progression, especially for asymptomatic patients, is unclear. Thus we reviewed 175 cases of metastatic AIPC from three randomized phase II clinical trials (docetaxel/thalidomide, docetaxel/vaccine, and ketoconazole/alendronate) at the National Cancer Institute between 1995 and 2004. The patients' PSA levels were assessed every 4 weeks, and CT and bone scans were done every 2-3 months. We retrospectively identified patients with bone metastasis only and examined subsequent CT for the occurrence of soft-tissue disease. For patients with progressive disease, we also examined bone scan and PSA progression.
Of 175 patients with metastatic prostate cancer, 105 (60%) had bone metastasis only, 12 (6.9%) had soft-tissue metastases only, and 58 (33.1%) had both bone and soft-tissue metastases. The median (range) follow-up was 8 (1-44) months for the 105 patients with bone metastasis only. During that time, two patients (1.9%) developed new soft-tissue disease; one developed right iliac fossa lymphadenopathy after 8 months and the other developed a perirectal mass after 12 months. The patient with new lymphadenopathy also had multiple new bone lesions identified by bone scan and PSA progression. The patient with the perirectal mass had PSA progression and a palpable abnormality.
This review of patients with AIPC and bone metastasis only, followed for a median of 8 months on clinical trials, shows that the incidence of asymptomatic new soft-tissue disease as the only sign of disease progression is quite low. Therefore, routine CT to exclude new soft-tissue disease in this population appears to be unwarranted. We recommend that for these patients CT is done only at the time of disease progression, as shown by bone scan, PSA level, or clinical presentation. We do not exclude the possibility that patients who remain on trial for significantly longer periods might benefit from routine interval CT.
BJU International 04/2007; 99(3):525-8. DOI:10.1111/j.1464-410X.2006.06654.x · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A phase I study was conducted to assess the safety of adoptive immunotherapy using gene-modified autologous T cells for the treatment of metastatic ovarian cancer.
T cells with reactivity against the ovarian cancer-associated antigen alpha-folate receptor (FR) were generated by genetic modification of autologous T cells with a chimeric gene incorporating an anti-FR single-chain antibody linked to the signaling domain of the Fc receptor gamma chain. Patients were assigned to one of two cohorts in the study. Eight patients in cohort 1 received a dose escalation of T cells in combination with high-dose interleukin-2, and six patients in cohort 2 received dual-specific T cells (reactive with both FR and allogeneic cells) followed by immunization with allogeneic peripheral blood mononuclear cells.
Five patients in cohort 1 experienced some grade 3 to 4 treatment-related toxicity that was probably due to interleukin-2 administration, which could be managed using standard measures. Patients in cohort 2 experienced relatively mild side effects with grade 1 to 2 symptoms. No reduction in tumor burden was seen in any patient. Tracking 111In-labeled adoptively transferred T cells in cohort 1 revealed a lack of specific localization of T cells to tumor except in one patient where some signal was detected in a peritoneal deposit. PCR analysis showed that gene-modified T cells were present in the circulation in large numbers for the first 2 days after transfer, but these quickly declined to be barely detectable 1 month later in most patients. An inhibitory factor developed in the serum of three of six patients tested over the period of treatment, which significantly reduced the ability of gene-modified T cells to respond against FR+ tumor cells.
Large numbers of gene-modified tumor-reactive T cells can be safely given to patients, but these cells do not persist in large numbers long term. Future studies need to employ strategies to extend T cell persistence. This report is the first to document the use of genetically redirected T cells for the treatment of ovarian cancer.
Clinical Cancer Research 11/2006; 12(20 Pt 1):6106-15. DOI:10.1158/1078-0432.CCR-06-1183 · 8.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the majority of pheochromocytomas (PHEO) are benign, a subset is malignant. Computed tomography (CT) and magnetic resonance imaging (MRI) localize PHEO with high sensitivity but, because of limited specificity, [(131)I]- or [(123)I]-metaiodobenzylguanidine ([(131)I]- or [(123)I]-MIBG) is often used as a complementary agent. 6-[18F]-fluorodopamine ([18F]-DA) has been developed as a radiopharmaceutical for the targeting of noradrenergic pathways, and has been shown to result in a better detection rate of PHEO sites than MIBG; however, [18F]-DA has shown a lack of accumulation in some patients with metastatic PHEO.
Five patients with widespread metastatic PHEO who had CT and MRI evidence of metastatic disease (one man and four women; age range, 25-64 years), and who underwent imaging with [(123)I]-MIBG, [18F]-DA and 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG), were evaluated retrospectively. Tomographic imaging was performed and positron emission tomography (PET) images were inspected visually and quantitatively.
All five patients had [(123)I]-MIBG scans that grossly underestimated the extent of disease when compared with conventional CT and MRI. All lesions seen on [(123)I]-MIBG scans were detected on [18F]-DA scans, which also detected additional lesions. Nonetheless, [18F]-DA also failed to detect numerous lesions seen on CT and MRI. In all of these cases, [18F]-FDG PET showed lesions that were not detected on either [(123)I]-MIBG or [18F]-DA scans.
When [(123)I]-MIBG or [18F]-DA fails to localize lesions seen on conventional imaging studies, [18F]-FDG may be recommended as an ancillary test for the diagnosis and localization of metastatic PHEO. This is particularly important in patients with aggressive PHEO.
Nuclear Medicine Communications 02/2006; 27(1):31-6. DOI:10.1097/01.mnm.0000189780.54658.e8 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autoimmune lymphoproliferative syndrome (ALPS) is associated with mutations that impair the activity of lymphocyte apoptosis proteins, leading to chronic lymphadenopathy, hepatosplenomegaly, autoimmunity, and an increased risk of lymphoma. We investigated the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) in discriminating benign from malignant lymphadenopathy in ALPS. We report that FDG avidity of benign lymph nodes in ALPS can be high and, hence, by itself does not imply presence of lymphoma; but FDG-PET can help guide the decision for selecting which of many enlarged nodes in ALPS patients to biopsy when lymphoma is suspected.
American Journal of Hematology 02/2006; 81(2):81-5. DOI:10.1002/ajh.20523 · 3.80 Impact Factor