Gracinda Costa

Stimulated Thyroglobulin at Recombinant Human TSH-Aided Ablation Predicts Disease-free Status One Year Later

CONTEXT Thyroglobulin (Tg) levels measured at the time of remnant ablation after thyroid hormone withdrawal (THW) were shown to have prognostic value in predicting disease-free status. OBJECTIVES Our objectives were to determine whether stimulated Tg levels, measured at the time of remnant ablation performed under recombinant human TSH (rhTSH) stimulation, has value in predicting absence of detectable disease 1 year after radioiodine therapy and to compare the results obtained with this approach with a cohort of patients submitted to ablation after THW. DESIGN This was a prospective observational study. SETTING AND PATIENTS The study included 293 consecutive patients treated for a differentiated thyroid carcinoma with no initial evidence of distant metastasis. All patients were submitted to a total or near-total thyroidectomy, followed by ablation either under rhTSH (n = 151) or endogenous TSH stimulation (n = 142). Patients with positive Tg antibodies were excluded. MAIN OUTCOME MEASURES The predictive value of Tg at ablation was assessed by receiver operating characteristic curve analysis. RESULTS In the rhTSH group, 96 patients (73.3%) were considered disease-free at 1 year. Stimulated Tg at ablation after rhTSH was found to be an independent prognostic indicator of disease persistence 12 months later. The highest-accuracy cutoff value for absence of detectable disease was defined as 7.2 ng/mL, with a negative predictive value of 90%. In the THW group, Tg at ablation also proved to have independent predictive value. Using the same threshold (7.2 ng/mL), the negative predictive value of Tg was 95% in the THW group. CONCLUSIONS When rhTSH was used, stimulated Tg at ablation had independent predictive value for disease-free status 1 year later. A low stimulated Tg at rhTSH-aided ablation may be considered a favorable prognosis factor.

TERT, BRAF and NRAS in primary thyroid cancer and metastatic disease.

Context Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype. Objectives To evaluate the frequency of TERT promoter (TERTp), BRAF, and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNMs), and distant metastases. Design and Patients Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTCs; n = 180), including 196 LNMs and 56 distant metastases. All the distant metastases included corresponded to radioiodine-refractory metastatic tissue. Results We found the following mutation frequency in primary PTCs, LNMs, and distant metastases, respectively: TERTp: 12.9%, 10.5%, and 52.4%; BRAF: 44.6%, 41.7%, and 23.8%; and NRAS: 1.2%, 1.3%, and 14.3%. There was a significant concordance between the primary tumor genotype and the corresponding LNM for all the genes, in particular BRAF-mutated PTC. The overall concordance between primary tumors and respective distant metastases was low. In the group of patients with PTCs, we found a high frequency of TERTp mutations and a low frequency of BRAF mutations in distant metastases, in comparison with the paired primary tumors. When present in distant metastases, BRAF mutations frequently coexisted with TERTp mutations. Conclusions When the genotype of primary tumors is compared with the genotype of LNMs, the concordance is high for all the genes studied. On the other hand, distant metastases show an enrichment in TERTp mutations and a decrease in BRAF mutations. TERTp mutations may play a role in distant metastases.

Persistent primary hyperparathyroidism: an uncommon location for an ectopic gland - Case report and review

Primary hyperparathyroidism (PHPT) is a common endocrine disorder that mainly affects middle-aged women. Patients are usually asymptomatic. The disease might be ascribable to hyperplasia, carcinoma, and single or multiple adenomas. PHPT may be sporadic or familial, the latter comprising multiple endocrine neoplasia type 1 or 2A, familial benign hypocalciuria hypercalcemia, and hyperparathyroidism-jaw tumor syndrome. The most common causes for persistent PHPT are multiglandular disease, and missed abnormal ectopic or orthotopic parathyroid glands. Imaging localization studies should precede a new surgical intervention. Ectopic parathyroid glands are rarely located at the aortopulmonary window. For diagnosis confirmation, (99m)Tc-sestamibi SPECT/CT seems to be an advantageous test. Another possibility is to perform (99m)Tc-sestamibi followed by thoracic CT or MRI. Parathyroidectomy may be performed by means of median sternotomy, thoracotomy, or video-assisted thoracoscopy. We describe a case of persistent primary hyperparathyroidism due to the presence of an ectopic parathyroid gland found at the aortopulmonary window. As the investigation necessary to clarify the etiology of recurrent nephrolithiasis proceeded, the diagnosis of PHPT was determined. The patient underwent subtotal parathyroidectomy; nevertheless, PHPT persisted. Genetic syndromes that could account for this condition were excluded. Imaging studies available at that time were not able to locate abnormal glands; moreover, the patient refused to undergo surgical exploration. Later, the patient underwent (99m)Tc-sestamibi SPECT/CT, which revealed a parathyroid gland at the aortopulmonary window.

Detection of Vaccinia virus during an outbreak of exanthemous oral lesions in Brazilian equids

REASONS FOR PERFORMING STUDY In August 2014, an outbreak of oral exanthematous disease in equids was reported in Brazil, affecting 11 donkeys and 3 mules. OBJECTIVES To investigate if Vaccinia virus (VACV) was the aetiological agent in this outbreak. STUDY DESIGN Investigation of clinical cases using serological, molecular and phylogenetic approaches. METHODS To analyse the presence of neutralising antibodies against VACV, samples were submitted in triplicate to a plaque-reduction neutralisation test (PRNT50% ). On the basis of previous studies which detected VACV DNA in sera, we submitted extracted DNA samples to different polymerase chain reaction (PCR) platforms targeting Orthopoxvirus (OPV) genes (C11R, A56R and A26L). The PCR products were directly sequenced in both orientations using specific primers and capillary electrophoresis. The alignment and phylogenetic analysis of the A26L and A56R nucleotide sequences (maximum likelihood) were prepared with the obtained nucleotide fragments. RESULTS Serological and molecular data suggested VACV as the aetiological agent. The neutralising antibodies against OPV were detected in 5 (55.5%) of the equids, with titres ≥40 neutralising u/ml. Based on the results obtained from all PCR platforms, all samples were positive for OPV: 9 (100%) for A56R, 4 (44.4%) for C11R and 3 (33.3%) for A26L. The alignment of the nucleotide sequences of the A26L and A56R fragments revealed that the samples were highly similar to the homologous genes from other Brazilian VACV Group 1 isolates (98.8% identity on average). Furthermore, both the A26L and A56R sequences showed signature deletions also present in the sequences of Group 1 VACV isolates from Brazil. CONCLUSIONS Our data raises questions about the role of equids in the chain of VACV epidemiology. The surveillance of equids in VACV-affected areas worldwide is relevant.

18F-FDG PET/CT in lung cancer. The added value of quantification

OBJECTIVE To test a software application for the quantification of metabolic heterogeneity and to evaluate its superiority in relation to visual interpretation. To investigate if a quantitative analysis adds information to the interpretation of 18F-FDG-PET/CT. MATERIAL AND METHODS The study analyzed 215 patients with a 18F-FDG-PET/CT done for the initial staging of lung cancer between March 2011 and December 2015. The study included 57 (26.5%) women and 158 (73.5%) men, with ages ranging from 34 to 88 years (mean±SD: 67.23±10.04). There were 82 surgical stages (I, II, IIIA), and 133 non-surgical stages (IIIB, IV). The primary tumour was analyzed quantitatively by obtaining the following parameters: SUVmax, metabolic active tumour volume (MATV), total lesion glycolysis (TLG), and the entropy heterogeneity index (ET). Heterogeneity was assessed visually. Death dates and/or the follow-up time were registered, ranging from 0.70 to 67.60 months (mean±SD: 23.20±17.68). RESULTS In multivariate analysis, ET emerged as a better predictor of survival than visual analysis of heterogeneity that was not statistically significant. The C-index determination demonstrated that all quantitative parameters were statistically-significant predictors of survival. Cut-offs were obtained in order to compare survival times. A multivariate analysis was performed. In the total population, the best predictor was the TNM stage, but MATV, ET, and male gender were statistically significant and independent predictors of survival. In stages without surgical indication, the best predictor was the TNM stage, but the MATV and male gender were statistically significant and independent predictors of survival. In the surgical stages, ET was the only statistically significant and independent predictor of survival. CONCLUSIONS Quantification adds prognostic information to the visual analysis of 18F-FDG-PET/CT.

Superiority of 18F-FNa PET/CT for Detecting Bone Metastases in Comparison with Other Diagnostic Imaging Modalities

INTRODUCTION The 18F-NaF positron emission tomography/computed tomography is being considered as an excellent imaging modality for bone metastases detection. This ability was compared with other imaging techniques. MATERIAL AND METHODS We retrospectively evaluated 114 patients who underwent 18F-NaF positron emission tomography/ computed tomography. Of these, 49 patients also had bone scintigraphy, 61 18F-FDG positron emission tomography/computed tomography and 10 18F-FCH positron emission tomography/computed tomography. We identified the technique that detected the largest number of bone metastases. For the detection of skeletal metastases with the 18F-NaF positron emission tomography/computed tomography study, the contribution of the positron emission tomography component was compared with the contribution of the computed tomography component. Cases in which 18F-NaF positron emission tomography/computed tomography and bone scintigraphy required further additional tests for diagnosis clarification were registered. RESULTS The 18F-NaF positron emission tomography/computed tomography was superior to bone scintigraphy in 49% of the patients (p < 0.001); it was superior to 18F-FDG positron emission tomography/computed tomography in 59% of the patients (p < 0.001) and it was superior to 18F-FCH positron emission tomography/computed tomography in 40% of the patients (p < 0.001). None of the compared imaging techniques were superior to 18F-NaF positron emission tomography/computed tomography. The positron emission tomography component was superior to computed tomography in 35% of the cases (p < 0.001). Further investigation was suggested in only 3.5% of patients who underwent 18F-NaF positron emission tomography/computed tomography (45% for bone scintigraphy) (p < 0.001). DISCUSSION As with other authors, our experience also confirms that 18F-NaF positron emission tomography/computed tomography is an excellent imaging modality for the detection of bone metastases, detecting lesions in more patients and more lesions per patient. CONCLUSION The 18F-NaF positron emission tomography/computed tomography showed a superior ability for the detection of bone metastases when compared with bone scintigraphy, 18F-FDG positron emission tomography/computed tomography and 18F-FCH positron emission tomography/computed tomography.

Rest myocardial perfusion imaging: a valuable tool in ED

BACKGROUND Acute chest pain is a frequent cause of emergency department (ED) visits. Rest myocardial perfusion imaging (RMPI) during or immediately after an episode of chest pain can provide diagnostic and prognostic information concerning acute coronary syndromes. AIM Our purpose was to evaluate the RMPI score in risk stratification of chest pain suspected to be of cardiac ischemic origin and negative troponin assessment. METHODS Ninety-six patients without an ongoing myocardial infarction or a history of coronary artery disease and in whom RMPI was performed in the ED because of chest pain suspected to be related with acute myocardial ischemia were included. Follow-up was performed considering the occurrence of death, myocardial infarction, or revascularization in a 12-month period admission. RESULTS Fourteen (14.6%) patients had events. According to survival analysis, the variables related with events were a history of angina (hazard ratio [HR], 4.5; P ≤ .01), an ischemic electrocardiogram (HR, 4.0; P ≤ .01), the abnormal RMPI (HR, 11.4; P ≤ .05), and the RMPI score (HR, 1.1; P ≤ .0001). When the variables of interest were forced into a multivariate model, the χ(2) associated with the model that includes clinical and electrocardiogram information was 16.3 (P ≤ .005) and in the model that also includes RMPI score, it was 23.0 (P ≤ .0005). CONCLUSION In a low- to intermediate-risk group of patients with suspected acute myocardial ischemia, RMPI gives not only diagnostic information but adds prognostic value to the traditional ED risk stratification tools.

Characterization of spermatogonial cells and niche in the scorpion mud turtle (Kinosternon scorpioides)

Undifferentiated spermatogonia (Aund) or spermatogonial stem cells (SSCs) are committed to the establishment and maintenance of spermatogenesis and fertility throughout a males life and are located in a highly specialized microenvironment called niche that regulates their fate. Although several studies have been developed on SSCs in mammalian testis, little is known about other vertebrate classes. The present study is the first to perform a more detailed investigation on the spermatogonial cells and their niche in a reptilian species. Thus, we characterized Aund/SSCs and evaluated the existence of SSCs niche in the Kinosternon scorpioides, a freshwater turtle found from Mexico to northern and central South America. Our results showed that, in this species, Aund/SSCs exhibited a nuclear morphological pattern similar to those described for other mammalian species already investigated. However, in comparison to other spermatogonial cell types, Aund/SSCs presented the largest nuclear volume in this turtle. Similar to some mammalian and fish species investigated, both GFRA1 and CSF1 receptors were expressed in Aund/SSCs in K. scorpioides. Also, as K. scorpioides Aund/SSCs were preferentially located near blood vessels, it can be suggested that this niche characteristic is a well conserved feature during evolution. Besides being valuable for comparative reproductive biology, our findings represent an important step towards the understanding of SSCs biology and the development of valuable systems/tools for SSCs culture and cryopreservation in turtles. Moreover, we expect that the above-mentioned results will be useful for reproductive biotechnologies as well as for governmental programs aiming at reptilian species conservation.

The value of quantitative analysis in 18F-NaF PET/CT

AIM To evaluate the ability of SUVmax to differentiate bone metastases from degenerative lesions, blastic from lytic metastases, as well as to determine the correlation between SUVmax with 18F-NaF and with 18F-FDG. MATERIAL AND METHODS A review was performed on 115 18F-NaF PET/CT studies. Of the 64 patients with bone metastases, 49 (39 women, 10 men, 61±12 years (16-81)), in whom the PET/CT supported the diagnosis of bone metastases, were selected for analysis. A record was made of the SUVmax of a maximum of ten metastases in each patient (total 172: 141 blastic, 31 lytic), as well as four degenerative lesions (total 188) with the greatest 18F-NaF uptake intensity. Of the 49 patients analyzed, 43 also had a 18F-FDG PET/CT performed in which a record was made of the SUVmax values for 18F-FDG calculated in the locations corresponding to the bone metastases observed in the 18F-NaF PET/CT: 128 metastases (106 blastic, 22 lytic). RESULTS The mean of the SUVmax values was significantly higher in metastases than in degenerative lesions, 26.8±17.3 vs. 15.3±6.3 (P<0.001) and in blastic than in lytic metastases, 27.9±18.3 vs. 22.1±11.3 (P=0.03). A SUVmax value above 42 always represented metastases, with all values above 49 representing blastic metastases. Using the SUVmax values, it was possible to predict the occurrence of metastases (AUC=0.723; P<0.001; 95% CI=0.671-0.776). The mean of the SUVmax with 18F-NaF was significantly higher in blastic metastases (27.9±18.3 vs. 22.1±11.3, P=0.03), whereas with 18F-FDG it was significantly higher in lytic ones (3.9±3.4 vs. 9.6±3.3; P<0.01). CONCLUSIONS SUVmax can contribute to the differentiation of metastases from degenerative lesions, and blastic from lytic metastases.

PET/CT with 18F-Fluorocholine in Patients with Prostatic Cancer in Biochemical Recurrence

INTRODUCTION In prostate cancer, after therapy with curative intent, biochemical recurrence frequently occurs. The purpose of this study was to evaluate the impact of PET/CT with 18F-fluorocholine in restaging these patients and in their orientation, and to analyze the effect of the risk stratification, the values of PSA and the hormone suppression therapy, in the technique sensitivity. MATERIAL AND METHODS Retrospective analysis of 107 patients with prostate carcinoma in biochemical recurrence who underwent PET/CT with 18F-fluorocholine in our hospital, between December 2009 and May 2014. RESULTS The overall sensitivity was 63.2% and 80.0% when PSA > 2 ng/mL. It was possible to identify distant disease in 28% of the patients. The sensitivity increased from 40.0%, in patients with low and intermediate risk, to 55.2% in high-risk patients. Without hormonal suppression therapy, the sensitivity was 61.8%, while in the group under this therapy, was 67.7%. DISCUSSION PET/CT with 18F-fluorocholine provided important information even in patients with low levels of PSA, however, with significantly increased sensitivity in patients with PSA > 2 ng/mL. Sensitivity was higher in high-risk patients compared with low and intermediate risk patients, however, without a statistically significant difference. The hormone suppression therapy does not appear to influence uptake of 18F-fluorocholine in patients resistant to castration. CONCLUSIONS In this study, PET/CT with 18F-Fluorocholine showed good results in restaging patients with prostate cancer biochemical recurrence, distinguishing between loco regional and systemic disease, information with important consequences in defining the therapeutic strategy.