Predictive Role of Serum Thyroglobulin after Surgery and before Radioactive Iodine Therapy in Patients with Thyroid Carcinoma.

INTRODUCTION: Thyroidectomy followed by radioactive iodine therapy (RAI) is the treatment of choice for differentiated thyroid carcinoma (DTC). Serum thyroglobulin (Tg) measurement has proved to be useful for predicting persistent and/or recurrent disease during follow-up of DTC patients. In our study, we evaluated the risk of disease recurrence in patients with papillary thyroid carcinoma (PTC), who were treated with thyroidectomy and RAI, by measuring serum Tg at different time-points: at least 40 days after surgery, in euthyroidism with TSH < 1.5 and usually 30 days before RAI (Tg-30), on the day of RAI (Tg0), and seven days after RAI (Tg+7). METHODS: One hundred and twenty-nine patients with PTC were enrolled in this retrospective study. All patients were treated with 131I for thyroid remnant ablation. Disease relapse (nodal disease or distant disease) during at least 36 months follow-up was evaluated by serum measurements of Tg, TSH, AbTg at different time points and by imaging techniques (neck ultrasonography, 131I-whole body scan (WBS) after Thyrogen® stimulation). Typically, patients were assessed at 3, 6, 12, 18, 24, and 36 months after RAI. We classified patients in five groups: (i) those who developed nodal disease (ND), (ii) those who developed distant disease (DD), (iii) those with biochemical indeterminate response and minimal residual thyroid tissue (R), (iv) those with no evidence of structural or biochemical disease + intermediate ATA risk (NED-I), and (v) those with no evidence of structural or biochemical disease + low ATA risk (NED-L). ROC curves for Tg were generated to find potential discriminating cutoffs of Tg values in all patients' groups. RESULTS: A total of 15 out of 129 patients (11.63%) developed nodal disease and 5 (3.88%) distant metastases, during the follow-up. We found that Tg-30 (with suppressed TSH) has the same sensitivity and specificity than Tg0 (with stimulated TSH), and it is slightly better than Tg+7, which can be influenced by the size of the residual thyroid tissue. CONCLUSION: Serum Tg-30 value, measured in euthyroidism 30 days before RAI, is a reliable prognostic factor to predict future nodal or distant disease, thus allowing to plan the most appropriate therapy and follow-up.

Analysis of Short-Term and Stable DNA Damage in Patients with Differentiated Thyroid Cancer Treated with 131I in Hypothyroidism or with Recombinant Human Thyroid-Stimulating Hormone for Remnant Ablation.

It is well known that ionizing radiation can induce genetic damage and that oxidative stress is a major factor inducing it. Our aim was to investigate whether thyroid remnant ablation with low activities of 131I (1,850 MBq) is associated with DNA damage by evaluating the CometAssay, micronuclei, and chromosome aberrations with multicolor fluorescent in situ hybridization. Methods: We studied 62 patients prepared with recombinant human thyroid-stimulating hormone (rhTSH) or by thyroid hormone withdrawal. In both groups, we analyzed stable and unstable genetic alterations before 131I therapy and 1 wk and 3 mo after 131I administration. We also correlated the genetic damage with several variables, including the degree of radiation-induced oxidative stress, genetic polymorphisms of enzymes involved in DNA repair, and antioxidative stress. Results: We found a comparable amount of DNA breaks evaluated by CometAssay and micronuclei testing in both groups of patients at different time points, but there was a significant increase in stable chromosome aberrations evaluated by multicolor fluorescent in situ hybridization (breaks and translocations) in patients prepared with thyroid hormone withdrawal. Overall, high chromosome damage was associated with higher retained body radioactivity and unfavorable gene polymorphism. A high level of free oxygen radicals and a low level of antioxidants were found in all patients at any time point. In particular, patients prepared with thyroid hormone withdrawal, at 3 mo, had significantly higher levels of free oxygen radicals than those prepared with rhTSH. Conclusion: An increase in stable chromosome aberrations with respect to baseline is detectable after administration of low doses of 131I in patients prepared with thyroid hormone withdrawal but not in patients prepared with rhTSH. The clinical significance of these chromosomal alterations remains to be determined.

Long-term metabolic evolution of brain metastases with suspected radiation necrosis following stereotactic radiosurgery: longitudinal assessment by F-DOPA PET.

BACKGROUND: The evolution of radiation necrosis (RN) varies depending on the combination of radionecrotic tissue and active tumor cells. In this study, we characterized the long-term metabolic evolution of RN by sequential PET/CT imaging with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (F-DOPA) in patients with brain metastases following stereotactic radiosurgery (SRS). METHODS: Thirty consecutive patients with 34 suspected radionecrotic brain metastases following SRS repeated F-DOPA PET/CT every 6 months or yearly in addition to standard MRI monitoring. Diagnoses of local progression (LP) or RN were confirmed histologically or by clinical follow-up. Semi-quantitative parameters of F-DOPA uptake were extracted at different time points, and their diagnostic performances were compared with those of corresponding contrast-enhanced MRI. RESULTS: Ninety-nine F-DOPA PET scans were acquired over a median period of 18 (range: 12-66) months. Median follow-up from the baseline F-DOPA PET/CT was 48 (range 21-95) months. Overall, 24 (70.6%) and 10 (29.4%) lesions were classified as RN and LP, respectively. LP occurred after a median of 18 (range: 12-30) months from baseline PET. F-DOPA tumor-to-brain ratio (TBR) and relative standardized uptake value (rSUV) increased significantly over time in LP lesions, while remaining stable in RN lesions. The parameter showing the best diagnostic performance was rSUV (accuracy = 94.1% for the optimal threshold of 1.92). In contrast, variations of the longest tumor dimension measured on contrast-enhancing MRI did not distinguish between RN and LP. CONCLUSION: F-DOPA PET has a high diagnostic accuracy for assessing the long-term evolution of brain metastases following SRS.

Dorsolateral Prefrontal Cortex Impairment in Methoxetamine-Induced Psychosis: An 18F-FDG PET/CT Case Study.

Novel psychoactive substances (NPSs) have currently become a major public health concern because of relatively easy accessibility to these compounds and difficulty in identifying them with routine laboratory techniques. Here, we report the 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) case study of a 23-year-old man who developed a substance-induced psychotic disorder after having intravenously injected himself with an unspecified amount of methoxetamine (MXE), a ketamine derivative hallucinogen. From a clinical perspective, a blunted affective responsiveness with diminished social drive and sense of purpose, along with a profound detachment from the environment, was observed. Psychometric and neuropsychological assessments highlighted severe dissociative symptoms and lack of motivation, along with a mild impairment of verbal fluency, working memory, and attention. Patient's 18F-FDG PET/CT scans displayed a significant bilateral deficit of tracer uptake within the dorsolateral prefrontal cortex (DLPFC). DLPFC activity is critical to goal-oriented cognitive functions, including working memory and sustained attention. DLPFC is also involved in both the temporal integration across multiple sensory modes and in the volitional control of actions, leading to the possibility to construct logically coherent temporal configurations of thought, speech, and behavior. This report highlights that a single acute MXE intoxication may produce severe brain impairment.

Thyro-gastric autoimmunity in patients with differentiated thyroid cancer: a prospective study.

Thyro-gastric autoimmunity has not been previously evaluated in patients with differentiated thyroid cancer (DTC), although its long-term complications may be relevant for the management of DTC patients. We assessed the prevalence of gastric autoimmunity and autoimmune gastritis (AG) in patients with Hashimoto's thyroiditis (HT) and concomitant DTC. Prevalence of parietal cell antibody (PCA) positivity, iron deficiency anemia (IDA), and pernicious anemia (PA) were prospectively assessed in 150 DTC patients referred for radioiodine ablation after total thyroidectomy. Patients were classified as HT (n = 31) and non-HT (n = 119) based on a combination of serological, ultrasonographic, and histological findings. Patients with PCA positivity were subsequently addressed to endoscopy for confirmation of atrophy body gastritis, required for the diagnosis of AG. For all the variables under study, a comparison between groups was made using Fisher's exact test and appropriate parametric and non-parametric tests. PCA positivity was significantly more prevalent in HT than in non-HT patients (12.9 vs 1.6 %, p = 0.017). After Hp eradication, a reversal of PCA positivity was observed in 3/4 patients in the HT group. IDA and PA did not differ significantly between groups. In the HT group, only one patient had endoscopical confirmation of mild gastric corporal atrophy. Gastric autoimmunity shows higher prevalence in patients with DTC and concomitant HT than in patients with DTC alone; however, in most cases, PCA positivity was associated with Hp infection. Furthermore, although previous reports found up to one-third of patients with HT to have associated AG, in our cohort AG was extremely rare.

Treatment with octreotide LAR in clinically non-functioning pituitary adenoma: results from a case-control study.

Surgical cure cannot be achieved in most patients with invasive non-functioning pituitary macroadenoma (NFPA). Short-term residual tumor treatment with somatostatin analogs has produced disappointing results. This prospective case-control study assessed the efficacy of chronic treatment with long acting octreotide (octreotide LAR) on tumor volume in patients harboring post-surgical NFPA residue. The study population comprised 39 patients with NFPAs not cured by surgery. All patients underwent somatostatin receptor scintigraphy at least 6 months after the last surgery. Patients with a positive pituitary level octreoscan at (n = 26) received octreotide LAR (20 mg every 28 days) for ≥ 12 months (mean follow-up 37 ± 18 months) (Treated group). Moreover, a fragment of tumor tissue from patients in the treated group was retrospectively collected to assess the immunohistochemical expression of somatostatin receptor subtypes (SSTRs). The patients with a negative octreoscan (n = 13) formed the control group (mean follow-up 37 ± 16 months). Hormonal, radiological and visual field parameters were periodically assessed. In the treated group, all tumors expressed at least one SSTR subtype. The SSTR5 subtype was the most abundant, followed by SSTR3. The tumor residue increased in five of 26 patients (19%) in the treated group and in seven of 13 controls (53%). Visual field and pituitary function did not change in any patient. This study indicates that SSTR5 and SSTR3 are the most frequently expressed SSTR subtypes in NFPAs and supports a potential role of SSTR subtypes in stabilization of tumor remnant from NFPAs.

Efficacy of the combined cabergoline and octreotide treatment in a case of a dopamine-agonist resistant macroprolactinoma.

Prolactinomas in males can be voluminous macroadenomas invading the surrounding structures. Medical therapy with dopamine agonists (the treatment of choice for these tumours) may be ineffective in the case of pharmacological resistance. In such cases, even surgical and/or radiation therapy cannot be curative due to the invasive potential of the adenoma. Hence, the appropriate therapeutic approach for these tumours is still a relevant clinical problem for endocrinologists. We report the history of an adolescent male who was diagnosed with a large invasive macroprolactinoma in 2002. He had severe bitemporal hemianopsia and hypopituitarism; prolactin levels at diagnosis were higher than 8,000 ng/ml. Medical therapy with cabergoline was initiated and resulted in decreased prolactin levels but not complete normalisation (maximal tolerated dose 3 mg/day). However, due to the worsening of the visual defect, the patient was operated in July 2004 through the trans-nasal approach and 2 years later through both the transcranial and the transphenoidal approaches. After the second surgery, a significant reduction of tumour mass was obtained. Immunohistochemistry for somatostatin receptors (sstr) subtypes showed a positive staining with the anti-sstr5 antibody. A scintigraphy with 111In-pentetreotide (Octreoscan) revealed a very intense tracer uptake in the sellar region. The administration of long-acting octreotide was initiated. After 12 months of therapy, prolactin levels normalised for the first time. Pituitary MRI did not reveal any tumor progression during a 2-year follow-up. This is a case of an invasive dopamine-resistant macroprolactinoma that was successfully controlled by extensive surgery and combined treatment with cabergoline and octreotide. The expression and functionality of sstr should be investigated in these tumours since a combined therapy with cabergoline and octreotide may be a good therapeutic course of action for select cases.

Radioimmunotherapy of heavily pre-treated, non-Hodgkin's lymphoma patients: efficacy and safety in a routine setting.

UNLABELLED: The aim of the present study waw to assess efficacy and safety of radio-immunotherapy with Zevalin (RIT-Z) in heavily pre-treated, rituximab-refractory patients. PATIENTS AND METHODS: We studied 12 patients with indolent lymphoma and 7 with aggressive lymphoma. The median number of prior rituximab-containing treatments was 2; overall, 3 therapies had been previously given. Ten patients received RIT-Z as salvage therapy, 9 at high risk of relapse received RIT-Z as consolidation. Staging and follow-up were obtained by positron-emission tomography. Outcomes assessed were failure-free survival (FFS) and time to next treatment (TTNT). RESULTS: Overall FFS and TTNT were 5 and 11 months, respectively; median follow-up 13 months. Major findings were i) no long-term remissions observed in 7 patients who had not responded to their most recent therapy and ii) lack of association between any pre-therapy variables analysed and outcomes. Different subgroups showed no difference in terms of toxicity. CONCLUSION: We encourage the use of RIT-Z as a consolidation for pre-treated patients with both indolent and aggressive lymphoma.

Central and peripheral dopamine transporter reduction in Parkinson's disease.

OBJECTIVE: Previous reports showed the reduction of dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinson's disease. In this work, we sought to investigate the possible correlation between central and peripheral dopamine transporter immunoreactivity values in a group of 11 drug-naive patients with Parkinson's disease. METHODS: Densitometric measurements of dopamine transporter immunoreactivity in peripheral blood lymphocytes was accomplished as described recently, using a monoclonal antidopamine transporter antibody. Dopamine transporter binding in the caudate and putamen nuclei was measured by means of (123)I-fluopane single-photon emission computed tomography in the same patients. RESULTS: The results failed to show any significant correlation between dopamine transporter immunoreactivity in peripheral blood lymphocytes and the caudate or putamen dopamine transporter binding. Moreover, dopamine transporter immunoreactivity in peripheral blood lymphocytes was reduced also in the single patient with normal striatal dopamine transporter binding. DISCUSSION: These results indicate the lack of correlation between central and peripheral dopamine transporter reduction in Parkinson's disease, using the methodologies applied herein. They therefore suggest that the two phenomena are unlikely to share a common pathogenetic mechanism.

High-resolution, hand-held camera for sentinel-node detection.

BACKGROUND: The imaging probe (IP) is a high-resolution (HR), 1-in(2) field-of-view hand-held gamma camera. We used it to detect breast cancer sentinel node (SN). PATIENTS AND METHODS: We divided 120 T1 breast cancer patients, who underwent Anger camera lymphoscintigraphy (ACL), in two subgroups of 60 patients who were age, body mass index, and cancer size matched: subgroup A (SA) and B (SB). SN was detected with a common gamma probe (GP) in SA, with IP plus GP in SB. RESULTS: Surgeons removed radioactive nodes without exceeding four nodes. Eighty-two (82) SNs were taken off in SA and 105 in SB (p<0.01). Of SA, 22 of 60 patients and 36 of 60 patients of SB showed more than 1 node, and 3 of them showed 3 nodes and 1 showed 4 nodes. Thirteen (13) patients resulted N(+) (21.6%) in SA. Ten (10) patients of SA showed an invasion on the hottest nodes and 3 on the second nodes. In the SB, 18 patients (25%) showed invasion. Sixteen (16) invasions were on hot, 4 on second, and 1 on the third node. Withdrawal time of SN was 11.25+/-4.7 minutes for SA and 7.4+/-2.8 minutes for SB (p<0.025). CONCLUSIONS: SN biopsy with IP is fast and discovers more SNs and more invasions than ACL.