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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.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.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.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.

Glioblastoma is one of the most aggressive cancers, but the molecular evolution is still not fully understood. We used PET imaging combined with deep sequencing of glioblastoma biopsies at both the RNA and DNA levels to get a deeper insight into molecular evolution. In the clinical setting, PET imaging provides information about metabolically active tumor areas, but the molecular interpretation is unclear. Our primary objective was to perform an intratumoral spatial comparison of biopsies from potentially aggressive and less aggressive areas in glioblastomas according to PET scans. Additionally, tissue from the tumor periphery was included. We used MRI, 11C-methionine(MET) PET, and 18F-FDG PET was used in combination to obtain a series of neurosurgical stereotactic biopsies from tumor areas with high MET and 18F-FDG uptake (hotspot), low MET and 18F-FDG uptake (coldspot), as well as tumor periphery of six glioblastoma patients that were processed for whole genome, exome, and transcriptome sequencing. Differential gene expression and gene ontology analysis showed that hotspots were enriched in gene sets associated with DNA replication, cell cycle, and ligand receptor interaction. Genome and exome analysis suggested hotspots and coldspots to have similar mutational profiles. However, a limited number of hotspot-specific mutations and fusion transcripts indicated that hotspot tumor cells developed from coldspot cells and point at the potential role of hotspot driver genes in glioblastoma. Our findings reveal that hotspots in glioblastomas represent a more advanced stage of molecular evolution than coldspots.

Glioblastoma is one of the most aggressive cancers, but the molecular evolution is not fully understood. We used PET imaging combined with deep sequencing of glioblastoma biopsies at both the RNA and DNA levels to get a deeper insight into molecular evolution. In the clinical setting, PET imaging provides information about metabolically active tumor areas, but the molecular interpretation is unclear. Our primary objective was to perform an intratumoral spatial comparison of biopsies from potentially aggressive and less aggressive areas in glioblastomas according to PET scans. We used MRI co-registered with 11C-MET-PET (amino acid) and 18F-FDG PET (glucose) in order to obtain representative neurosurgical stereotactic biopsies from tumor areas with high accumulation of these two metabolites (hotspot), low accumulation (coldspot), and no accumulation as the periphery of six glioblastoma patients that were processed for whole genome, exome, and transcriptome sequencing. Differential gene expression and gene ontology analysis showed that hotspots were enriched in gene sets associated with DNA replication, cell cycle, and ligand-receptor interaction. Genome and exome analysis suggested hotspots and coldspots have similar mutational profiles. However, a limited number of hotspot-specific mutations and novel fusion transcripts indicated that hotspot-associated tumor cells developed from coldspot-associated tumor cells and point at the potential role of hotspot driver genes in glioblastoma evolution. Our findings reveal that hotspots in glioblastomas represent a more advanced stage of molecular evolution than coldspots. Citation Format: Atul Anand, Jeanette Krogh Petersen, Mark Burton, Martin Jakob Larsen, Lars van Andersen, Dylan Scott Harwood, Christian Bonde Pedersen, Frantz Rom Poulsen, Peter Grupe, Torben A. Kruse, Mads Thomassen, Bjarne Winther Kristensen. Deeper insight into intratumoral heterogeneity by MRI and PET-guided stereotactic biopsies from glioblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3796.

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.

We have used sentinel lymph node biopsy (SLNB) for oral cancer patients since 2001. Our lymphoscintigraphic, surgical as well as the histopathological examination technique has developed and been refined over the last 15 years. We use three dimensional SPECT-CT images for high accuracy identification of the sentinel lymph nodes, a simple one incision surgical approach and frozen sectioning for fast histopathological evaluation of the lymph nodes. These refinements have enabled us to perform the sentinel lymph node procedure and neck dissection in the correct patients in a same day procedure in the majority of patients.

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.

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 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.

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-operatingcharacteristic (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.

Eur J Clin Invest 2010; 41 (7): 693–702 Abstract Background Lack of consensus regarding the antithyroid drug regimen in relation to radioiodine (131I) 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 131I 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 131I period, while serum-free T3 index was higher in the −BRT group (P

Background: Radioiodine (131|) therapy is widely used for treatment of non-toxic goiters. A limitation for this treatment is a low thyroid radioiodine uptake (RAIU), often encountered in these patients. Aim: To estimate the impact of various factors on the thyroid RAIU. Methods: We examined prospectively 170 patients (146 females; age range: 22–87 yrs) with nodular goiter (median 64 ml, range: 20–464 ml) selected for 131| therapy. Serum TSH was sub-normal in 42.4%. None were treated with anti-thyroid drugs. The thyroid RAIU was determined at 24h and 96h. The goiter volume was measured by ultrasound (no.=127), or by magnetic resonance imaging (no.=43). Results: The 24h and the 96h RAIU were 34.2±9.8(SD)% (range: 11.4–66.0%) and 34.0±10.0% (range: 10.5–60.9%), respectively. Sixty-one patients had a 24h RAIU

Introduction: The impact on tracheal anatomy and respiratory function of recombinant human (rh)TSH-stimulated 131I 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 131I 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 mm2 (P = 0.005 compared with 92 ± 38 mm2 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 131I therapy. In the long term, tracheal compression is diminished, and the inspiratory capacity improved, compared with 131I therapy alone.

Udgivelsesdato: 2007-Sep INTRODUCTION: The effect of (131)I therapy amplification by recombinant human (rh) TSH prestimulation in very large goiters has not been evaluated in a double-blinded, placebo-controlled study. METHODS: Twenty-nine patients (22 females; age range 37-87 yr) with a large multinodular goiter (median 160 ml, range 99-440 ml) were randomized to receive placebo (n = 15) or 0.3 mg rhTSH (n = 14) 24 h before (131)I administration. Goiter volume was monitored by magnetic resonance imaging. RESULTS: On average, the goiter volume was unchanged 1 wk after therapy in both groups, but the largest deviations from baseline were observed in the rhTSH group. After 12 months the median goiter volume was reduced from 170 to 121 ml in the placebo group and from 151 to 72 ml in the rhTSH group, respectively (within group: P = 0.001; between group: P = 0.019). This corresponds to reductions of 34.1 +/- 3.2 and 53.3 +/- 3.3%, respectively (between group: P < 0.001). In the placebo group, the goiter reduction correlated positively with the retained thyroid (131)I dose, whereas such a relationship was absent in the rhTSH group. Adverse effects, mainly related to thyroid pain and cervical compression, were more frequent in the rhTSH group. At 12 months, goiter-related complaints were significantly reduced in both groups without any between-group difference. One and three patients in the placebo and the rhTSH group, respectively, developed hypothyroidism. CONCLUSION: rhTSH-stimulated (131)I therapy improves the reduction of very large goiters by more than 50%, compared with (131)I therapy alone, but at the expense of more adverse effects after therapy. Our data suggest that rhTSH stimulation may work through mechanisms that go beyond the increase in thyroid (131)I uptake

Objective: To compare the efficacy of interstitial laser photocoagulation (ILP) with radioiodine in hot thyroid nodules. Design: Thirty consecutive outpatients with subclinical or mild hyperthyroidism and a scintigraphically solitary hot nodule with extraglandular suppression were randomized to either one ILP session or one radioiodine (131I) dose. Methods: ILP was performed under continuous ultrasound-guidance and with an output power of 2.5–3.5 W. 131I was given as a single dose based on thyroid volume and a 24-h thyroid 131I uptake. Thyroid function and nodule volume were evaluated at inclusion and at 1, 3 and 6 months after treatment. Results: Normalization of serum TSH was achieved in 7 out of 14 patients in the ILP group and in all 15 patients in the 131I group (P=0.0025). In the ILP group, mean thyroid nodule volume reduction was 44±5% (s.e.m.; P131I group 47±8% (PP=0.73). The mean reduction of total thyroid volume was 7±5% in the ILP group (P=0.20) and 26±8% (P=0.006) in the 131I group (P=0.06 between-group). Two patients in the 131I group developed hypothyroidism but no major side effects were seen. Conclusions: This first randomized study, comparing ILP with standard therapy, demonstrates that ILP and 131I therapy approximately halves thyroid nodule volume within 6 months; but in contrast to 131I, extranodular thyroid volume is unaffected by ILP and no patient developed hypothyroidism. Using the present design, ILP seems inferior to 131I therapy in normalization of serum TSH. The potential value of ILP as a non-surgical alternative to 131I needs further investigation.

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.

Purpose: To validate lymphatic mapping combined with sentinel lymph node biopsy as a staging procedure, and to evaluate the possible clinical implications of added oblique lymphoscintigraphy and/or tomography and test the intra- and interobserver reproducibility of lymphoscintigraphy. Material and Methods: Forty patients (17 F and 23 M, aged 32–90) with 24 T1 and 16 T2 squamous cell carcinoma of the oral cavity. Planar lymphoscintigraphy, emission and transmission tomography were performed. Detection and excision of the sentinel nodes were guided by a gamma probe. The sentinel nodes were step-sectioning and stained with hematoxylin and eosin and cytokeratin (CK 1). Histology and follow-up were used as “gold standard”. Tumor location, number of sentinel lymph nodes, metastasis, and recurrences were registered. Two observers evaluated the lymphoscintigraphic images to assess the inter-rater agreement. Results: Eleven (28%) patients were upstaged. The sentinel lymph node identification rate was 97.5%. Sentinel lymph node biopsy significantly differentiated between patients with or without lymph node metastasis ( P = 0.001). Lymphatic mapping revealed 124 hotspots and 144 hot lymph nodes were removed by sentinel lymph node biopsy. Three patients developed a lymph node recurrence close to the primary tumor site during follow-up. Added oblique lymphoscintigraphic images and/or tomography revealed extra hotspots in 15/40 (38%) patients. In 4/40 (10%), extra contralateral hotspots were detected. Conclusion: Sentinel lymph node biopsy upstaged 28% of the patients. Sentinel lymph nodes close to the primary tumor were difficult to find. Added oblique planar images and/or tomographic images revealed extra clinical relevant hotspots in 38% of patients. Reproducibility proved excellent.

Udgivelsesdato: 2004-Jul BACKGROUND: The aim was to determine the reliability and reproducibility of sentinel node biopsy (SNB) as a staging tool in head and neck squamous cell carcinoma (HNSCC) for T1/2 clinically N0 patients by means of a standardized technique. METHODS: Between June 1998 and June 2002, 227 SNB procedures have been performed in HNSCC cases at six centers. One hundred thirty-four T1/2 tumors of the oral cavity/oropharynx in clinically N0 patients were investigated with preoperative lymphoscintigraphy (LSG), intraoperative use of blue dye/gamma probe, and pathological evaluation with step serial sectioning and immunohistochemistry, with a follow-up of at least 12 months. In 79 cases SNB alone was used to stage the neck carcinoma, and in 55 cases SNB was used in combination with an elective neck dissection (END). RESULTS: In 125/134 cases (93%) a sentinel node was identified. Of 59 positive nodes, 57 were identified with the intraoperative gamma probe and 44 with blue dye. Upstaging of disease occurred in 42/125 cases (34%): with hematoxylin-eosin in 32/125 (26%) and with additional pathological staging in 10/93 (11%). The sensitivity of the technique with a mean follow-up of 24 months was 42/45 (93%). The identification of SNB for floor of mouth (FOM) tumors was 37/43 (86%), compared with 88/91 (97%) for other tumors. The sensitivity for FOM tumors was 12/15 (80%), compared with 30/30 (100%) for other tumor groups. CONCLUSION: SNB can be successfully applied to early T1/2 tumors of the oral cavity/oropharynx in a standardized fashion by centers worldwide. For the majority of these tumors the SNB technique can be used alone as a staging tool.

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.

(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.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.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 RAIU30%. All observers significantly underestimated the thyroid volume if this was80 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.Thyroid (99m)Tc scintigraphy has poor interobserver agreement and is inaccurate for assessment of quantitative thyroid parameters, even when performed by experienced specialists.This study was supported by grants from the Danish Agency for Science, Technology and Innovation.not relevant.

Introduction: 99mTc-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 131I 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 99mTc scintigraphy has poor interobserver agreement and is inaccurate for assessment of quantitative thyroid parameters, even when performed by experienced specialists.

Background: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ( 131I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with 131I 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 96.0mL; range 31.9-242.2mL) were randomized to receive placebo (n=32), 0.01mg MRrhTSH (n=30), or 0.03mg MRrhTSH (n=33) 24 hours before a calculated 131I 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 0.03mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01mg 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 0.01mg MRrhTSH group, and 53±18.6% in the 0.03mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03mg MRrhTSH group, the subset of patients with basal 131I uptake 131I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤0.03mg, indicating that the lower threshold for efficacy is around this level.

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

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.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.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).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.

Background: Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). Objective, Design, and Setting: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. Patients and Intervention: Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. Main Outcome Measures: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. Results: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. Conclusion: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.

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. 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. 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. Based on clinical and angiographic findings, the marked improvements after CABG in cardiac perfusion and function are poorly predicted. Keywords: Coronary artery bypass grafting; Coronary artery disease; Myocardial perfusion scintigraphy.

Lack of consensus regarding the antithyroid drug regimen in relation to radioiodine ((131) I) therapy of hyperthyroidism prompted this randomized trial comparing two strategies.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 (P0·05). 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).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.

Udgivelsesdato: 2010-Aug Context and Objective: Stimulation with recombinant human TSH (rhTSH) before radioiodine ((131)I) 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 (131)I-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 (131)I uptake, but per se potentiates the effect of (131)I-therapy, allowing a major reduction of the (131)I-activity without compromising efficacy. This approach is attractive in terms of minimizing posttherapeutic restrictions and in reducing the potential risk of radiation-induced malignancy.

Udgivelsesdato: 2009

Udgivelsesdato: 2009-May 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.

INTRODUCTION: Referrals from practising physicians to hospital departments are of varying quality. This increases the risk of inappropriate or even incorrect patient treatment courses. We examined the quality of referrals to a large department of nuclear medicine before and after initiatives aimed at improving the information and feedback to the practising physicians. MATERIALS AND METHODS: An evaluation of the quality of referrals (n = 579) from praticising physicians to the Department of Nuclear Medicine, Odense University Hospital, Denmark, recorded during two periods of three months each before and after (1) publication of a referral guideline and (2) a feedback response to those physicians whose referrals were insufficient. A general practitioner (GP) and a specialist in nuclear medicine (NM) judged independently whether the referrals were good, acceptable or unacceptable. RESULTS: During the two periods, 281 and 298 referrals were received, respectively. Of these, 37% and 27%, respectively, were from practising specialists (PSs). After intervention, 23% more referrals were received from GPs, and the share of "good" referrals also increased (before/after: 48%/72% (GP), 61%/84% (NM)). In contrast, there was a 23% decrease in referrals from PSs, whereas the share of "good" referrals remained unchanged or increased (before/after: 64%/66 % (GP), 64%/96% (NM)). In addition, there was a change in the referral pattern from both GPs and PSs. CONCLUSION: Relatively simple and inexpensive intervention caused an increase in the number and quality of referrals from GPs and a fall in referrals from PSs without an obvious improvement in quality. Udgivelsesdato: 2006-Apr-3

Use of recombinant human thyrotropin increases the thyroid radioiodine (iodine 131 [(131)I]) uptake and may have a role in the context of (131)I therapy of benign goiter.In a double-blind, placebo-controlled trial, 57 patients with nodular nontoxic goiter (51 women and 6 men) were randomized to receive either 0.3 mg of recombinant human thyrotropin (n = 28) or placebo (n = 29) 24 hours before (131)I therapy. The (131)I dose was calculated based on thyroid size (measured by ultrasound), thyroid (131)I uptake, and (131)I half-life. The follow-up period was 1 year and included measurements of thyroid size and function and patient satisfaction.Baseline median goiter volume was 51 mL (range, 20-99 mL) in the placebo group and 59 mL (range, 25-92 mL) in the thyrotropin group (P = .75). At 12 months, the mean +/- SEM relative goiter reduction was 46.1% +/- 4.0% in the placebo group and 62.1% +/- 3.0% in the thyrotropin group (P = .002 between groups). The difference was most pronounced among patients with large goiters. Within each group, there was no significant correlation between retained thyroid (131)I dose and goiter reduction. Adverse effects were significantly more frequent in the thyrotropin group (34 vs 12 events; P.001). Permanent hypothyroidism developed in 3 patients (11%) in the placebo group compared with 16 patients (62%) in the thyrotropin group (P.001). Patient satisfaction was high and uninfluenced by the use of recombinant human thyrotropin.Stimulation with recombinant human thyrotropin prior to (131)I therapy improves thyroid size reduction by 35%, with a 5-fold higher rate of hypothyroidism. These effects are, at least partially, mediated through mechanisms other than an increase in retained (131)I thyroid dose. Further recombinant human thyrotropin dose-finding studies are warranted before routine use.

Purpose: To compare sentinel lymph node biopsy, magnetic resonance imaging (MRI), Doppler ultrasonography, and palpation as staging tools in patients with T1/T2 N0 cancer of the oral cavity. Material and Methods: Forty consecutive patients were enrolled (17 F and 23 M, aged 32–90 years), 24 T1 and 16 T2 cN0 squamous cell carcinoma of the oral cavity. Palpation was carried out by two observers prior to inclusion. MRI, gray-scale and Doppler ultrasonography were performed. Lymphoscintigraphies were done after peritumoral injections of 99mTc labelled rheniumsulphide nanocolloid, followed by sentinel lymph node biopsy guided by a gamma probe and Patent Blue. Palpation, Doppler ultrasonography, MRI, and sentinel lymph node biopsy were compared to a combination of histopathology and follow-up. Diagnostic testing was performed using the x2 test. Results: Histopathological examination revealed metastatic spread to the neck in 14 of 40 patients. One patient had bilateral neck disease. Sentinel lymph node biopsy and ultrasonography were performed in 80 neck sides of 40 patients and MRI in 70 neck sides (5 patients were claustrophobic). SN revealed suspicious lymph nodes in 12 necks, ultrasonography in 23 necks, and MRI in 9 necks. The positive predictive value of sentinel lymph node biopsy was 100%, ultrasonography 57%, and MRI 56%. The respective negative predictive values were 96%, 96%, and 85%. The sensitivity of sentinel lymph node biopsy 80% was comparable to ultrasonography 87%, but the sensitivity of MRI 36% was low. The specificities were 100%, 85%, and 93%, respectively. By combined sentinel lymph node biopsy and ultrasonography the overall sensitivity could have been 100%. Conclusion: Sentinel lymph node biopsy improved staging of patients with small N0 oral cancers. Combined sentinel lymph node biopsy and Doppler ultrasonography may further improve staging. MRI and simple palpation results were poor.

Udgivelsesdato: 2004-Aug Attenuation correction may improve the diagnostic accuracy of myocardial perfusion imaging (MPI). However, few studies have dealt with the clinical consequences for reporting. We compared routine reports based on scatter-corrected MPI (MPI-routine) with consensus readings of scatter-corrected (MPI-scatter) and scatter plus attenuation-corrected studies (MPI-attenuation) to investigate the impact of attenuation correction on reporting. One hundred consecutive stable angina patients (including 55 men) were investigated in a 99mTc-sestamibi 2-day gated protocol with scatter and attenuation correction. With MPI-routine, 53 patients had normal perfusion and 47 abnormal perfusion, compared to 62 and 38 with MPI-attenuation, and 54 and 46, respectively, with MPI-scatter. Agreement between MPI-routine and MPI-attenuation with respect to overall diagnosis (normal/abnormal perfusion) was 89% (kappa=0.78) compared to 95% (kappa=0.90) between MPI-routine and MPI-scatter. With MPI-attenuation, the overall routine diagnosis changed in 11 patients, of which ten cases were judged normal after scatter plus attenuation correction. The majority of the "normalised" studies were among patients with apparently single-vessel RCA disease as judged from MPI. Agreement rates with regard to normal, reversible or irreversible defects between MPI-attenuation and MPI-routine for the LAD, LCX and RCA territories were 88%, 97% and 85%, respectively, without significant sex differences. In conclusion, attenuation correction caused a change in diagnosis in approximately 10% of the patients, corresponding to one-fifth of the abnormal studies. In all but one case, the shift was from abnormal to normal, mostly because of a different interpretation in the RCA territory.

Udgivelsesdato: null-null BACKGROUND: Observer variability of dual-isotope myocardial perfusion imaging (MPI) with single photon emission computed tomography has rarely been investigated. The aim of our study was to evaluate the interpretive reproducibility with this technique. METHODS AND RESULTS: We report on 507 patients with known or suspected stable angina who were studied before coronary angiography. A 1-day thallium 201/technetium 99m sestamibi rest/stress MPI protocol was used. MPI was interpreted by 2 independent observers without knowledge of clinical data, using a 20-segment scoring model. By consensus, the overall rate of abnormal MPI was 49% (59% in men and 34% in women). The interobserver agreement for the whole group (kappa = 0.85) and for men and women separately (kappa = 0.86 and 0.82, respectively) was excellent with regard to the overall diagnosis (normal, reversible, or fixed defects) as well as left anterior descending and left circumflex artery vascular territories (kappa = 0.85 and 0.82, respectively). However, in the right coronary artery territory, agreement was excellent in men (kappa = 0.83) but moderate in women (kappa = 0.57). CONCLUSIONS: In a relatively large group of men and women with stable angina pectoris, interpretive reproducibility (overall and individual vessel diagnosis) was excellent, except in the right coronary artery territory of women, in which it was moderate.

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.