Dynamic multi-pinhole collimated brain SPECT of Parkinson's disease by [123I]FP-CIT: a feasibility study of fSPECT.

We investigated the feasibility of using a dopamine transporter (DaT) tracer ligand ([123I]FP-CIT) along with novel multi-pinhole brain collimators for dynamic brain single photon emission computed tomography (SPECT) in suspected Parkinson's disease patients. Thirteen patients underwent dynamic tracer acquisitions before standard imaging. Uptake values were corrected for partial volume effects. Specific binding ratio (SBRcalc) was calculated, reflecting binding potential relative to non-displaceable binding (BPND) in the cortex. Additional pharmacokinetic parameters (BPND, R1, k2) were estimated using the simplified reference tissue model, revealing differences between Kahraman low-score (LS) and high-score (HS) groups. Results showed increasing striatal tracer uptake until 100 min post-injection, with consistent values afterward. Uptake and SBRcalc ratios matched visual assessment. LS patients had lower putamen than caudate nucleus tracer uptake, decreased BPND values, while R1 and k2 values were comparable to HS patients. In conclusion, dynamic multi-pinhole SPECT using DaT tracer with the extraction of pharmacokinetic parameters is feasible and could help enable early differentiation of reduced and normal DaT values.

Organ-specific accuracy of [18F]FDG-PET/CT in identifying immune-related adverse events in patients with high-risk melanoma treated with adjuvant immune checkpoint inhibitor.

PURPOSE: This study aimed to determine the organ-specific accuracy of [18F]FDG-PET/CT in identifying immune-related adverse events (irAEs) in patients with high-risk (stage III/IV) surgically resected melanoma treated with an adjuvant immune checkpoint inhibitor (ICI) and determine the incidence of irAEs within the first year after starting treatment. MATERIALS AND METHODS: This registry-based study included individuals who had undergone surgical removal of melanoma and were undergoing adjuvant ICI treatment (either nivolumab or pembrolizumab). The study specifically enrolled patients who had undergone both a baseline and at least one subsequent follow-up [18F]FDG-PET/CT scan. Follow-up scans were performed every third month in the first year after surgery to screen for disease recurrence. We retrospectively compared the follow-up scans with baseline scans to identify irAEs. Clinical information on irAEs was obtained from medical records and served as a reference standard for determining the accuracy of [18F]FDG-PET/CT. RESULTS: A total of 123 patients with 363 [18F]FDG-PET/CT scans were included, and 65 patients (52.8%) developed irAEs. In decreasing order, the organ-specific incidences of irAEs were: skin 26/65 (40%), muscle and joints 21/65 (32.3%), intestines 13/65 (20%), thyroid gland 12/65 (18.5%), lungs 4/65 (6.2%), and heart 2/65 (3.1%). The sensitivities and specificities of [18F]FDG-PET/CT for diagnosing irAEs were: skin 19% (95% CI: 7-39%) and 95% (88-98%), muscles and joints 71% (48-89%) and 83% (75-90%), intestines 100% (75-100%) and 85% (77-91%); thyroid gland 92% (62-99%) and 95% (89-98%), lungs 75% (19-99%) and 90% (83-95%), and heart 50% (13-99%) and 97% (92-99%), respectively. CONCLUSION: [18F]FDG-PET/CT generally had moderate to high sensitivities (except for skin and heart) and specificities in diagnosing irAEs in patients receiving adjuvant ICI; this could be suggested to be systematically assessed and reported in scan reports.

"Visualization" of pain using cerebral 18F-FDG PET/CT following surgical treatment of lumbar disc herniation.

PURPOSE: We hypothesized that unilateral leg pain following surgical treatment of lumbar disc herniation (LDH) is associated with an increase in the glucose metabolism of the contralateral thalamus. METHODS: Patients scheduled for surgery due to LDH underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography less than two weeks prior to surgery. Their thalamic FDG uptake was measured and expressed as the mean and partial volume corrected mean standardized uptake values (SUVmean and cSUVmean). These measures were compared with patient-related outcome measures collected pre- and 1-year post-operatively: back and leg pain on a 0-100 VAS scale and health-related quality of life as measured by the EuroQol-5D (EQ-5D). RESULTS: Twenty-six patients (ten females) aged 49.7 ± 7.4 (mean ± SD) years were included. There was a significant correlation between painful body side and increased contralateral thalamic uptake of FDG, with regard to cSUVmean values. Correlation analyses including clinical parameters and cSUVmean indicated some association with 1-year change in EQ-5D. CONCLUSION: These preliminary data sustain the hypothesis that unilateral pain in patients with LDH is associated with increased glucose metabolism in the contralateral thalamus, suggesting a central role of thalamus in chronic pain perception.

The diagnostic accuracy and clinical impact of FDG-PET/CT follow-up for patients on adjuvant immunotherapy for high-risk malignant melanoma.

OBJECTIVE: The benefit of FDG-PET/CT in follow-up of patients treated with adjuvant immunotherapy after resection of high-risk malignant melanoma (MM) is debated. This study evaluated the diagnostic accuracy and clinical impact of FDG-PET/CT for diagnosing MM recurrence during the first year after surgery. METHODS: We retrospectively included 124 patients with resected high-risk MM, who received adjuvant immunotherapy and follow-up FDG-PET/CT. Clinical information and AJCC-8 stage was obtained from patients' medical records. Recurrence was verified by biopsy/progression on a subsequent scan leading to change of treatment. Non-recurrence was assumed when no metastases were observed until the subsequent follow-up scan. Incidence of recurrence, sensitivity, specificity, positive and negative predictive values (PPV and NPV) were outcome measures. RESULTS: Incidence rate of MM recurrence was 0.27 [95% CI 0.17-0.37] per person-year during the first-year. Recurrence was detected in 13 patients (10%) at 3-month FDG-PET/CT, in 10 patients (8.1%) at 6 months, 1 patient (0.8%) at 9 months, 3 patients (2.4%) at 12 months. The overall sensitivity, specificity, PPV, and NPV were 97% [86-99], 82% [78-86], 39% [29-50], and 99% [98-99], respectively. The PPV trended towards higher values as disease stage increased. At the 3-month scan, the majority of actions derived from positive findings were surgery or earlier expedition of the subsequent follow-up scan. CONCLUSION: The high rate of recurrence in patients with high-risk MM treated with adjuvant immunotherapy emphasizes the need for follow-up. The potential harm by a moderately low specificity reflecting a high number of false-positive results must be weighed against the benefit of early detection of recurrence.

Diagnostic manifestations of total hemispheric glucose metabolism ratio in neuronal network diaschisis: diagnostic implications in Alzheimer's disease and mild cognitive impairment.

PURPOSE: We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHODS: We performed FDG-PET/CT in 23 patients (mean age 63.7 years, range 50-78, 17 females) diagnosed with AD (n = 15) or MCI (n = 8) during a six-month period in 2014. Ten neurologically healthy individuals (HIs) (mean age 62.5 years, range 43-75, 5 females) served as controls. A neuroimaging expert provided visual assessment of diaschisis. The total hemispheric glucose metabolism ratio (THGr) was calculated, and with area-under the curve of receiver operating characteristics (AUC-ROC) we generated a "Network Diaschisis Test (NDT)". RESULTS: The qualitative detection of cerebral (Ce) and cerebellar (Cb) diaschisis was 7/15 (47%), 0/8 (0%), and 0/10 (0%) in AD, MCI, and HI groups, respectively. Median cerebral THGr was 0.68 (range 0.43-0.99), 0.86 (range 0.64-0.98), and 0.95 (range 0.65-1.00) for AD, MCI, and HI groups, respectively (p = 0.04). Median cerebellar THGr was, respectively, 0.70 (range 0.18-0.98), 0.70 (range 0.48-0.81), and 0.84 (range 0.75-0.96) (p = 0.0138). A positive NDT yielded a positive predictive value of 100% for the presence of AD or MCI and a 86% negative predictive value for healthy brain. Moreover, the diagnostic manifestation of THGr between MCI and AD led to a positive predictive value of 100% for AD, but a negative predictive value of 42.9% for MCI. CONCLUSION: Patients with AD or MCI had more pronounced diaschisis, lateralized hemispheric glucose metabolism and lower THGr compared to healthy controls. The NDT distinguished AD and MCI patients from HIs, and AD from MCI patients with a high positive predictive value and moderate and low negative predictive values. THGr can be a straightforward source of investigating neuronal network diaschisis in AD and MCI and in other cerebral diseases, across institutions.

Total Thyroidectomy for Thyroid Cancer Followed by Thyroid Storm due to Thyrotropin Receptor Antibody Stimulation of Metastatic Thyroid Tissue.

BACKGROUND: Graves disease (GD) is an autoimmune condition characterized by the presence of antibodies against the thyrotropin receptor (TRAB), which stimulate the thyroid gland to produce excess thyroid hormone. Theoretically, TRAB could stimulate highly differentiated thyroid cancer tissue and/or metastases to produce thyroid hormone. CASE: A 68-year-old male, with weight loss and palpitations, was diagnosed with thyrotoxicosis. A later MRI, due to persistent shoulder pain, revealed multiple bone metastases. A biopsy was diagnostic for follicular variant of papillary thyroid carcinoma, and total thyroidectomy was performed. One week after thyroidectomy the patient was admitted with severe hyperthyroidism. TRAB was >40 IU/mL (normal <0.7 IU/mL). High-dose antithyroid drug treatment was followed by high-dose radioactive iodine-131 (RAI) and local radiotherapy covering the right shoulder. Antithyroid drug treatment continued until after the fourth RAI dose. Hypothyroidism did not occur until following the fifth RAI treatment. SUMMARY AND CONCLUSIONS: We present a patient initially diagnosed with thyrotoxicosis and subsequently with metastatic follicular variant of papillary thyroid cancer. It is suggested that TRAB stimulated the highly differentiated extrathyroidal metastatic thyroid tissue to produce excessive amounts of thyroid hormone, delayed diagnosis, and potential aggravation of the course of thyroid cancer.

Prognostic Implications of Total Hemispheric Glucose Metabolism Ratio in Cerebrocerebellar Diaschisis.

Diaschisis denotes brain dysfunction remote from a focal brain lesion. We have quantified diaschisis and investigated its prognostic value in glioma. Methods: We compared 50 18F-FDG PET/CT studies collected prospectively from 14 patients with supratentorial glioma (5 men and 9 women; age range, 35-77 y) with 10 single scans from healthy controls (age range, 43-75 y). Dedicated 3-dimensional segmentation software was used to obtain total hemispheric glucose metabolic ratios (THGr) by dividing total hemispheric 18F-FDG uptake in each diaschitic hemisphere-that is, the ipsilateral cerebral hemisphere (THGr(Ce)) and the contralateral cerebellar hemisphere (THGr(Cb))-by its respective contralateral side. Receiver-operating-characteristic (ROC) analysis was performed to determine optimal cut-offs for combinations of THGr(Ce) and THGr(Cb). Two independent observers obtained data for reproducibility analysis, and THGr values were compared with qualitative assessment of diaschisis performed by a PET neuroimaging specialist. Results: Qualitative analysis confirmed cerebrocerebellar diaschisis in all glioblastoma PET studies performed within 1 y of death. Healthy subjects had significantly higher THGr(Ce) values (P = 0.0007) and THGr(Cb) values (P = 0.02) than glioblastoma patients. ROC analysis yielded diaschisis thresholds of 0.62 for THGr(Ce) and 0.84 for THGr (Cb). Qualitative assessment demonstrated cerebral diaschisis in 16 of 17 (94%) cases with THGr(Ce) below the determined threshold and cerebellar diaschisis in 25 of 26 (96%) cases with THGr(Cb) below the determined threshold. When both THGr(Ce) and THGr(Cb) were below the ROC threshold, the combined diaschisis measures had a positive predictive value for survival below 1 y of 100%. When one parameter was below the threshold, it had a positive predictive value of 75%, and when both parameters exceeded thresholds, the negative predictive value for survival above 1 y was 79%. Median interrater variability was 3.3% and 5.9% for THGr(Ce) and THGr(Cb), respectively. Conclusion: The THGr measures demonstrated diaschisis in the cerebrum and cerebellum of patients with glioma. Combined cerebrocerebellar diaschisis ratios with ROC thresholds for both forebrain and hindbrain had high negative and positive predictive values for survival for less than a year. The THGr method allows comparison of data obtained at different institutions and is now open for further validation in gliomas and other cerebral diseases.

Dual-time-point Imaging and Delayed-time-point Fluorodeoxyglucose-PET/Computed Tomography Imaging in Various Clinical Settings.

The techniques of dual-time-point imaging (DTPI) and delayed-time-point imaging, which are mostly being used for distinction between inflammatory and malignant diseases, has increased the specificity of fluorodeoxyglucose (FDG)-PET for diagnosis and prognosis of certain diseases. A gradually increasing trend of FDG uptake over time has been shown in malignant cells, and a decreasing or constant trend has been shown in inflammatory/infectious processes. Tumor heterogeneity can be assessed by using early and delayed imaging because differences between primary versus metastatic sites become more detectable compared with single time points. This article discusses the applications of DTPI and delayed-time-point imaging.

Systemic oxidative stress to nucleic acids is unaltered following radioiodine therapy of patients with benign nodular goiter.

BACKGROUND: Little is known about the whole body oxidative stress burden following radioactive iodine ((131)I) therapy of thyroid diseases. METHODS: We studied 17 patients with benign nodular goiter treated with (131)I therapy. The targeted thyroid dose was 50 Gy in 11 patients pretreated with 0.1 mg of recombinant human TSH (rhTSH). In 6 patients, the applied thyroid dose was 100 Gy without rhTSH prestimulation. Well-established biomarkers of oxidative stress to RNA (8-oxo-7,8-dihydroguanosine; 8-oxoGuo) and DNA (8-oxo-7,8-dihydro-2'-deoxyguanosine; 8-oxodG) were measured in freshly voided morning urine (normalized against the creatinine concentration) at baseline, and 7 and 21 days after rhTSH (not followed by (131)I), and 7 and 21 days after (131)I therapy, respectively. RESULTS: The baseline urinary excretions of 8-oxoGuo and 8-oxodG were 2.20 ± 0.84 and 1.63 ± 0.70 nmol/mmol creatinine, respectively. We found no significant changes in the excretion of any of the metabolites, neither after rhTSH stimulation alone nor after (131)I therapy. Also, no significant differences were found between the rhTSH group (low dose, median (131)I: 152 MBq) and the non-rhTSH group (high dose, median (131)I: 419 MBq; 8-oxoGuo: p = 0.66, 8-oxodG: p = 0.71). CONCLUSION: Systemic oxidative stress, as detected by nucleic acids metabolites in the urine, is not increased after thyroid stimulation with 0.1 mg of rhTSH, or after (131)I therapy. Our method cannot quantify the oxidative stress induced locally in the thyroid gland, but the study supports that (131)I therapy of benign nodular goiter carries no or only a minute risk of developing subsequent malignancies. It remains to be explored whether our findings also apply to hyperthyroid disorders.

¹8F-fluorodeoxyglucose PET/computed tomography for primary brain tumors.

Structural imaging with computed tomography (CT) and MR imaging is the mainstay in primary diagnosis of primary brain tumors, but these modalities depend on morphologic appearance and an intact blood-brain barrier, and important aspects of tumor biology are not addressed. Such issues may be alleviated by (18)F-fluorodeoxyglucose (FDG)-PET and FDG-PET/CT imaging, which may provide clinically important information with regard to primary differentiation between tumor types, initial staging and risk stratification, therapy planning, response evaluation, and recurrence detection. This article describes some of the potential contemporary applications of FDG and PET in primary brain tumors.

Substantial interobserver variation of thyroid volume and function by visual evaluation of thyroid (99m)Tc scintigraphy.

INTRODUCTION: (99m)Tc-pertechnetate scintigraphy is much used in the evaluation of patients with nodular goitre. We investigated the ability of experienced observers to estimate the thyroid 24-h (131)I uptake (RAIU) and the thyroid volume by visual evaluation of the scintigram. MATERIAL AND METHODS: Two endocrinologists and two nuclear medicine specialists visually evaluated thyroid scintigrams from 171 patients with nodular goitre. The variables were assessed in a blinded fashion according to predefined categories and then compared with the true values. The assessments were repeated after four weeks. Kappa (κ ω) statistics were used. RESULTS: There was a low probability (range 6-22%) for the observers to assess the thyroid RAIU correctly. The probability of assessing the thyroid volume correctly was in the 14-22% range. Endocrinologists tended to underestimate the thyroid RAIU, mostly in patients with a RAIU > 30%. All observers significantly underestimated the thyroid volume if this was > 80 ml. There was a low interobserver agreement for the thyroid RAIU assessment (κ ω-values: 0.03-0.43) as well as for the thyroid volume assessment (κ ω-values: 0.19-0.48). The corresponding κ ω-values for the intraobserver agreement were 0.34-0.68 and 0.37-0.62, respectively. Nuclear medicine specialists achieved a significantly higher agreement than endocrinologists in their evaluation of both thyroid parameters. CONCLUSION: Thyroid (99m)Tc scintigraphy has poor interobserver agreement and is inaccurate for assessment of quantitative thyroid parameters, even when performed by experienced specialists. FUNDING: This study was supported by grants from the Danish Agency for Science, Technology and Innovation. TRIAL REGISTRATION: not relevant.

Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study.

BACKGROUND: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I therapy. METHODS: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2 ± 9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 mL; range 31.9-242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated (131)I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. RESULTS: At six months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH group, and 53 ± 18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal (131)I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH group (13.4 ± 23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of the study was favorable. CONCLUSIONS: When used as adjuvant to (131)I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤ 0.03 mg, indicating that the lower threshold for efficacy is around this level.

Prestimulation with recombinant human thyrotropin (rhTSH) improves the long-term outcome of radioiodine therapy for multinodular nontoxic goiter.

OBJECTIVE: The objective of the study was to evaluate the long-term outcome of recombinant human TSH (rhTSH)-augmented radioiodine ((131)I) therapy for benign multinodular nontoxic goiter. PATIENTS AND METHODS: Between 2002 and 2005, 86 patients with a multinodular nontoxic goiter were treated with (131)I in two randomized, double-blind, placebo-controlled trials. (131)I-therapy was preceded by 0.3 mg rhTSH (n = 42) or placebo (n = 44). In 2009, 80 patients completed a follow-up (FU) visit, including determination of thyroid volume, thyroid function, and patient satisfaction by a visual analog scale. RESULTS: In both groups, thyroid volume was further reduced from 1 yr to final FU (71 months). The mean goiter volume reductions obtained at 1 yr and final FU [59.2 ± 2.4% (sem) and 69.7 ± 3.1%, respectively] in the rhTSH group were significantly greater than those obtained in the (131)I-alone group (43.2 ± 3.7 and 56.2 ± 3.6%, respectively, P = 0.001 and P = 0.006), corresponding to a gain of 24% at final FU. At last FU the mean reduction in compression visual analog scale score was significantly greater in patients receiving rhTSH (P = 0.049). Additional therapy (thyroid surgery or (131)I) was required more often in the placebo group (nine of 44) compared with the rhTSH group (two of 42) (P = 0.05). The prevalence of hypothyroidism at 1 yr [9 and 43% in the placebo and rhTSH groups, respectively (P < 0.0001)] increased to 16 and 52%, respectively, at final FU (P = 0.001). CONCLUSION: Enhanced goiter volume reduction with rhTSH-augmented (131)I therapy improves the long-term reduction in goiter-related symptoms and reduces the need for additional therapy compared with plain (131)I therapy. Overall patient satisfaction is benefited, despite a higher rate of permanent hypothyroidism.

Can preoperative myocardial perfusion scintigraphy predict changes in left ventricular perfusion and function after coronary artery bypass graft surgery?

OBJECTIVES We wanted to evaluate whether preoperative myocardial perfusion scintigraphy (MPS) could predict changes in cardiac symptoms and postoperative myocardial perfusion and left ventricular function after coronary artery bypass grafting (CABG). METHODS Ninety-two patients with stable angina pectoris (and at least one occluded coronary artery) underwent MPS before, and 6 months after, undergoing CABG. The result of the MPS was kept secret from the surgeons. RESULTS Before CABG, 90% of the patients had angina. After CABG, 97% of the patients were without symptoms. Overall graft patency was 84%. Before CABG, one patient had normal perfusion; in the rest of them the defects were classified as follows: reversible (60%), partly reversible (27%) and irreversible (12%). Following CABG, 33% had normal perfusion; in the rest the defects were reversible in 29%, partly reversible in 12% and irreversible in 26%. Left ventricular ejection fraction (LVEF), which was normal before operation in 45%, improved in 40% of all patients. The increase in LVEF was not related to the preoperative pattern of perfusion defects. Of 30 patients with normalized perfusion after CABG, 29 (97%) had reversible defects and one patient had partly reversible defects. Of 83 perfusion defects, which were normalized after CABG, 67 were reversible (81%) or partly reversible (12%). Seventy-five percent of all reversible coronary artery territories before CABG were normalized after operation. CONCLUSIONS Our results indicate that reversible or partly reversible perfusion defects at a preoperative MPS have a high chance of normalized myocardial perfusion assessed by MPS 6 months after operation. Normal perfusion is obtained almost exclusively in territories with reversible ischaemia. Symptoms improved in nearly all patients and LVEF in a significant fraction of the patients, not related to preoperative MPS.

Angiography-based prediction of outcome after coronary artery bypass surgery versus changes in myocardial perfusion scintigraphy.

OBJECTIVES: The present study compared the clinical prediction of the effect of coronary artery bypass grafting (CABG) on coronary blood flow and left ventricular ejection fraction (LVEF) with changes in gated myocardial perfusion scintigraphy. METHODS: A prospective group of 92 patients underwent myocardial perfusion scintigraphy before and 6 months after CABG, the results being kept secret from the surgeon. Based on clinical and angiographic findings, the surgeons filled in a questionnaire indicating the predicted changes in coronary blood flow in each of the three coronary artery territories and in the LVEF. RESULTS: Symptomatic improvement was present in nearly all the patients. Following CABG, the perfusion defects were reduced in around two-thirds and normalized in one-third of the territories clinically predicted to improve. Improved perfusion for territories not predicted to improve was slightly lower, and correlations between predicted and observed regional changes in coronary blood flow and perfusion defects were poor. LVEF increased (by over five ejection fraction units) in almost half of the patients, but with no correlation between the predicted and the observed changes. CONCLUSIONS: Based on clinical and angiographic findings, the marked improvements after CABG in cardiac perfusion and function are poorly predicted.

Low risk of recurrence in breast cancer with negative sentinel node.

INTRODUCTION: The sentinel lymph node (SLN) procedure has emerged as a safe staging method with a low morbidity. The objective of the present study was to examine the recurrence rates including especially the axillary recurrence rate in SLN-negative patients after a long follow-up period. MATERIAL AND METHODS: A total of 344 breast cancer patients were referred to SLN biopsy at our department from January 2000 to May 2005. Lymphoscintigraphy with (99m)Tc-nanocolloid was followed by same-day radioprobe-guided surgery. Among the 344 patients, 181 were SLN-negative. The group of SLN-negative patients was followed with regard to recurrence in general and axillary recurrence in particular by reviewing their respective medical files from control visits. RESULTS: The identification rate (IR) was 99% (340/344). Extra-axillary SLNs were detected in seven patients (4%). One patient had an axillary recurrence 39 months after the primary operation, corresponding to an axillary recurrence rate of 0.6% after a median follow-up of 60 months (range 7-93). CONCLUSION: With a high IR and an axillary recurrence rate of 0.6% after five years of follow-up, our data suggest that the SLN procedure is a valid and accurate method for the staging of breast cancer patients.

A randomized trial evaluating a block-replacement regimen during radioiodine therapy.

BACKGROUND: Lack of consensus regarding the antithyroid drug regimen in relation to radioiodine ((131) I) therapy of hyperthyroidism prompted this randomized trial comparing two strategies. DESIGN: Patients with Graves' disease (GD, n = 51) or toxic nodular goitre (TNG, n = 49) were randomized to (131) I either 8 days following discontinuation of methimazole (-BRT, n = 52, median dose: 5 mg) or while on a continuous block-replacement regimen (+BRT, n = 48, median dose 15 mg methimazole and 100 µg levothyroxine). results: Patients in the +BRT group required more radioactivity. In this group, thyroid function did not change in the early post (131) I period, while serum-free T3 index was higher in the -BRT group (P < 0·05). One year posttherapy, the fraction of cured patients (euthyroid or hypothyroid) was 48% and 61% in the +BRT and -BRT group, respectively (P = 0·014 unadjusted; P = 0·004 adjusted), but the outcome depended on the type of disease. In GD, treatment failure in the +BRT group correlated positively with the 24-h thyroid (131) I uptake (P = 0·017), while no correlations existed in the -BRT group. In addition to +BRT allocation, patients with TNG were at higher risk of treatment failure with lower thyroid radiation doses (P = 0·048), higher doses of methimazole (P = 0·026) and lower levels of serum TSH (P = 0·009). CONCLUSIONS: A continuous block-replacement regimen results in a stable thyroid function during (131) I therapy but is hampered by the higher amounts of radioactivity required. The study demonstrates that the outcome in GD is highly unpredictable, while treatment failure in patients with TNG is correlated with a number of factors.

Recombinant human thyrotropin-stimulated radioiodine therapy of nodular goiter allows major reduction of the radiation burden with retained efficacy.

CONTEXT AND OBJECTIVE: Stimulation with recombinant human TSH (rhTSH) before radioiodine (131I) therapy augments goiter volume reduction (GVR). Observations indicate that rhTSH has a preconditioning effect beyond increasing thyroid (131)I uptake. We test the hypothesis that an equivalent GVR might be obtained by an absorbed thyroid dose well below what has been used previously. PATIENTS AND DESIGN: In a double-blinded setup, 90 patients (78 women; median age, 52 yr; range, 22-83) with a nontoxic nodular goiter (median size, 63 ml; range, 25-379 ml) were randomized to either 0.1 mg rhTSH (n=60) followed by a thyroid dose of 50 Gy or placebo followed by 100 Gy (n=30). RESULTS: At 12 months, the mean relative GVR in the placebo and the rhTSH group was identical (35+/-3%; P=0.81). The median administered 131I-activity was 170 MBq (45-1269) in the rhTSH group and 559 MBq (245-3530) in the placebo group (70% reduction, P<0.0001). According to the official radiation regulation, hospitalization was required in 14 patients in the placebo group vs. one patient in the rhTSH group (P<0.0001). In both groups, goiter-related symptoms were effectively relieved in the majority of patients. The prevalence of myxedema (10%) did not differ among groups. CONCLUSIONS: This is the first study to demonstrate that rhTSH not only increases the thyroid 131I uptake, but per se potentiates the effect of 131I-therapy, allowing a major reduction of the 131I-activity without compromising efficacy. This approach is attractive in terms of minimizing posttherapeutic restrictions and in reducing the potential risk of radiation-induced malignancy.

Optimizing 131I uptake after rhTSH stimulation in patients with nontoxic multinodular goiter: evidence from a prospective, randomized, double-blind study.

UNLABELLED: Prestimulation with recombinant human thyroid-stimulating hormone (rhTSH) augments radioiodine (131)I therapy for benign nontoxic multinodular goiter. The purpose of this study was to determine the optimal time interval between rhTSH and (131)I administration to enhance thyroid radioactive iodine uptake (RAIU). METHODS: Patients were randomized, in a 2-factorial design, to receive either a 0.1-mg dose of rhTSH (n = 60) or placebo (n = 30) and to a time interval of 24, 48, or 72 h before (131)I administration. The rhTSH- or placebo-stimulated RAIU study was performed at 4 wk after a baseline RAIU assessment in a tertiary referral center at a university hospital. A total of 90 patients (78 women; median age, 52 y; range, 22-83 y) referred to (131)I therapy for symptomatic nontoxic goiter (median goiter volume, 63 mL; range, 25-464 mL) were included in the study. Change in thyroid RAIU was determined at 24 and 96 h after (131)I tracer administration. RESULTS: In the placebo subgroups, RAIU did not change significantly from baseline. The mean (+/-SE) 24-h RAIU increased from 33.8% +/- 2.3% to 66.0% +/- 1.8% (111.2% increase) with a 24-h interval, from 36.8% +/- 2.1% to 64.6% +/- 2.7% (83.3% increase) with a 48-h interval, and from 33.0% +/- 2.7% to 49.6% +/- 2.5% (62.4% increase) with a 72-h interval. All within-group changes were highly significant (P < 0.001). The effect was negatively correlated with initial RAIU (r = -0.703, P < 0.001). The increase in 24- and 96-h RAIU was significantly higher in the rhTSH/24-h group than it was in the rhTSH/72-h group (P = 0.023 and 0.012, respectively) and insignificantly higher than in the rhTSH/48-h group (P = 0.37 and 0.26, respectively). CONCLUSION: The effect of rhTSH on thyroid RAIU is most pronounced when administered 24 h before (131)I administration and declines with longer time intervals. Whether there is a similar time dependency for goiter reduction after rhTSH-stimulated (131)I-therapy remains to be clarified.

Recombinant human thyrotropin-stimulated radioiodine therapy of large nodular goiters facilitates tracheal decompression and improves inspiration.

INTRODUCTION: The impact on tracheal anatomy and respiratory function of recombinant human (rh)TSH-stimulated (131)I therapy in patients with goiter is not clarified. METHODS: In a double-blinded design, patients (age 37-87 yr) with a large multinodular goiter (range, 99-440 ml) were randomized to placebo (n = 15) or 0.3 mg rhTSH (n = 14) 24 h before (131)I therapy. The smallest cross-sectional area of the trachea (SCAT; assessed by magnetic resonance imaging) and the pulmonary function were determined before, 1 wk, and 12 months after therapy. RESULTS: Data on goiter reduction have been reported previously. In the placebo group, no significant changes in the lung function or SCAT were found throughout the study. In the rhTSH group, a slight decrease was observed in the forced vital capacity 1 wk after therapy, whereas the mean individual change in SCAT was significantly increased by 10.5% (95% confidence interval = 0.9-20.0%). A further increase in SCAT to 117 +/- 36 mm(2) (P = 0.005 compared with 92 +/- 38 mm(2) at baseline) was seen at 12 months, corresponding to a mean of 31.4% (95% confidence interval = 16.0-46.8%). The expiratory parameters did not change significantly, whereas forced inspiratory flow at 50% of the vital capacity (FIF50%) increased from initially 3.34 +/- 1.33 liters/sec to ultimately 4.23 +/- 1.88 liters/sec (P = 0.015) in the rhTSH group, corresponding to a median increase of 24.6%. By 12 months, the relative improvements in FIF50% and in SCAT were inversely correlated to the respective baseline values (FIF50%: r = -0.47, P = 0.012; SCAT: r = -0.57, P = 0.001). CONCLUSION: On average, neither compression of the trachea nor deterioration of the pulmonary function was observed in the acute phase after rhTSH-augmented (131)I therapy. In the long term, tracheal compression is diminished, and the inspiratory capacity improved, compared with (131)I therapy alone.