Association of BRAF V600E Mutant Allele Proportion with the Dissemination Stage of Papillary Thyroid Cancer.

The early identification of aggressive forms of cancer is of high importance in treating papillary thyroid cancer (PTC). Disease dissemination is a major factor influencing patient survival. Mutation status of BRAF oncogene, BRAF V600E, is proposed to be an indicator of disease recurrence; however, its influence on PTC dissemination has not been deciphered. This study aimed to explore the association of the frequency of BRAF V600E alleles in PTC with disease dissemination. In this study, 173 PTC samples were analyzed, measuring the proportion of BRAF V600E alleles by qPCR, which was then normalized against the proportion of tumor cells. Semiquantitative analysis of BRAF V600E mutant protein was performed by immunohistochemistry. The BRAF V600E mutation was present in 60% of samples, while the normalized frequency of mutated BRAF alleles ranged from 1.55% to 92.06%. There was no significant association between the presence and/or proportion of the BRAF V600E mutation with the degree of PTC dissemination. However, the presence of the BRAF mutation was significantly linked with angioinvasion. This study's results suggest that there is a heterogeneous distribution of the BRAF mutation and the presence of oligoclonal forms of PTC. It is likely that the BRAF mutation alone does not significantly contribute to PTC aggressiveness.

SIMULTANEOUS METASTASES OF PAPILLARY THYROID CARCINOMA AND NEUROENDOCRINE TUMOR OF THE CECUM TO CERVICAL LYMPH NODES: A CASE REPORT.

We present a case of a patient with simultaneous cervical lymph node metastasis of papillary thyroid cancer (PTC) and cecum neuroendocrine tumor (NET). A 45-year-old male patient with the diagnosis of metastatic NET of the cecum underwent fine needle aspiration (FNA) of a positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET) positive nodule in the left thyroid lobe. Due to FNA finding suspect of PTC, the patient underwent total thyroidectomy with central neck dissection. Histopathologic finding revealed PTC of the left thyroid lobe and small solitary lymph node PTC metastasis in the central neck region. Postoperative evaluation with neck ultrasound (US) revealed two enlarged suspected lymph nodes in cervical regions III and IV on the left side of the neck and the patient underwent FNA with measurement of thyroglobulin (Tg) in the aspirates. The FNA finding of the cervical lymph node in the region III revealed PTC metastasis with high Tg value in the aspirate, while FNA finding of the cervical lymph node in the region IV revealed NET metastasis with low Tg value in the aspirate. Postoperative serum Tg value was 17.75 µg/L and the patient underwent 5550 MBq iodine-131 (I-131) therapy. A year after I-131 therapy, follow-up neck US demonstrated complete cure of PTC cervical lymph node metastasis in the region III and stable in size NET cervical lymph node metastasis in the region IV. To our knowledge, this is the first report of simultaneous occurrence of cervical lymph node metastases of PTC and NET of the cecum.

THE CONCENTRATION OF INTERLEUKIN 6 AND TUMOR NECROSIS FACTOR ALPHA IN SALIVA AND BLOOD OF PATIENTS WITH INACTIVE MULTIPLE SCLEROSIS AND COEXISTING HASHIMOTO'S THYROIDITIS.

The concentration of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the blood is higher in patients with active multiple sclerosis (MS) compared to those with inactive disease. The concentration of IL-6 and TNF-α in the blood is higher in patients with Hashimoto's thyroiditis (HT) compared to those with a healthy thyroid. The aim of the study was to assess whether serum IL-6 and TNF-α levels correlated with saliva in patients with inactive MS and whether there was a difference in these groups of patients depending of thyroid status. We also examined the correlation of thyroid stimulating hormone (TSH) levels with thyroid status. The study included 54 patients in the inactive phase of MS. The level of cytokines in the blood was determined by chemiluminescence, and in saliva by ELISA. Blood and saliva IL-6 levels showed positive correlation, while blood and saliva TNF-α levels were not correlated. There was a significantly higher TSH level in patients with inactive MS with positive thyroid antibodies, without therapy, compared with those with negative antibodies.

Psychiatric Illness or Immune Dysfunction-Brain Perfusion Imaging Providing the Answer in a Case of Anti-NMDAR Encephalitis.

BACKGROUND: We investigated the potential use of SPECT quantification in addition to qualitative brain perfusion analysis for the detection of anti-NMDAR encephalitis. The question is how to normalize brain activity to be able to quantitatively detect perfusion patterns. Usually, brain activity is normalized to a structure considered unaffected by the disease. METHODS: Brain [99mTc]-HMPAO SPECT was performed as a method to detect brain perfusion patterns. The patterns of abnormal brain perfusion cannot always be reliably and qualitatively assessed when dealing with rare diseases. Recent advances in SPECT quantification using commercial software have enabled more objective and detailed analysis of brain perfusion. The cerebellum and whole brain were used as the normalization structures and were compared with visual analysis. RESULTS: The quantification analysis performed with whole brain normalization confirmed right parietal lobe hypoperfusion while also detecting statistically significant left-to-right perfusion differences between the temporal lobe and thalamus. Whole brain normalization further described bilateral frontal lobe hyperperfusion, predominantly of the left lobe, and was in accordance with visual analysis. CONCLUSION: SPECT quantitative brain perfusion analysis, using the whole brain as the normalization structure rather than the cerebellum, in this case, improved confidence in the visual detection of anti-NMDAR encephalitis and provided unexpected solutions to atypical psychiatric dilemmas.

99mTc-MIBI SPECT/CT SCINTIGRAPHY AND ULTRASOUND OF THE ANTERIOR NECK REGION IN DIAGNOSING PARATHYROID GLAND PATHOLOGY IN PATIENTS WITH THYROID NODULES.

Parathyroid scintigraphy with 99mTc-MIBI is an imaging technique used in nuclear medicine and performed in patients with suspected hyperparathyroidism (HPT). The objective of this study was to evaluate the role of this technique in patients who, along with suspected HPT, also have thyroid nodules. Retrospective analysis included a period of 8 years (2006-2013). The study included 91 patients with clinical or laboratory suspected HPT. Pathologic changes in parathyroid glands were demonstrated in 47 (70%) of 67 patients with positive scintigraphy. Pathologic changes in parathyroid glands were not evident in the remaining 20 (30%) patients. Out of nine patients with negative scintigraphy results but with suspected enlargement of the parathyroid gland examined by ultrasound, eight (89%) patients did not show pathologic changes in the parathyroid gland, whereas one (11%) patient had evident changes. Eight (54%) of 15 patients with suspected scintigraphy had positive ultrasound findings, as well as fine needle aspiration cytology (FNAC) findings with parathyroid hormone (PTH) determination in the aspirate. Seven (46%) patients had negative FNAC findings and PTH in the aspirate. The study showed scintigraphy to have high sensitivity (98%) in detecting patients with pathologic changes in the parathyroid glands. In patients with suspected HPT, scintigraphy needs to be combined with FNAC and PTH determination in the aspirate due to its low specificity of 28%.

Improvements of Frontotemporal Cerebral Blood Flow and Cognitive Functioning in Patients With First Episode of Schizophrenia Treated With Long-Acting Aripiprazole.

PURPOSE/BACKGROUND: Frontal and temporal cerebral blood flow (CBF) changes are the most common impairments of CBF described in patients with schizophrenia. Those impairments have also been associated with cognitive deficits, a hallmark of schizophrenia. In light of that fact, treatment interventions should target cognitive deficits to prevent chronic disability. However, specific therapies targeting cognitive symptoms are very few and far between. One of the treatment possibilities is aripiprazole, because several studies reported its potential procognitive effects. The objective of this study was to investigate whether use of aripiprazole in its long-acting injectable formulation (ALAI), during a 3-month treatment, has beneficial effects on CBF and cognitive functioning in patients with first episode of schizophrenia. METHODS/PROCEDURES: Single-photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime was performed at 2 time points. Cognitive functions were assessed with a standardized test for cognitive functions, 5-KOG test, whereas severity of clinical symptoms was assessed with the Positive and Negative Syndrome Scale, both at the same 2 time points as single-photon emission computed tomography. Three-month treatment with ALAI was associated with improvement of several cognition indices and improvements of right-sided frontal and temporal CBF, as well as of clinical symptoms. FINDINGS/RESULTS: Multivariate tests were used to test for the effects of ALAI treatment on cognitive functions, clinical presentation, and brain perfusion in a 3-month period. Multivariate model revealed statistical significance (F = 11.958, P < 0.001). Of 10 separate 5-KOG parameters, 3-month treatment with ALAI significantly influenced 4: undelayed recall, delayed recall, attention, and working memory-digit span forward. Finally, 3-month ALAI treatment significantly improved regional CBF in 2 of 4 investigated areas, both on the right side of the brain (frontally and temporally). IMPLICATIONS/CONCLUSIONS: Results of this research showed that treatment with ALAI in patients with first episode of schizophrenia is associated with improved right-sided frontal and temporal CBF, as well as with improved symptoms, including cognition indices. Although we cannot confirm it directly, it is possible that improved frontotemporal CBF led to the improvement in cognition indices.

Thyroglobulin Measurement in Needle Aspiration for Detection of Recurrences and Neck Metastases in Patients with Differentiated Thyroid Carcinoma: Significance of Anti-Tg Antibodies.

The worldwide incidence of differentiated thyroid cancer (DTC) has increased in recent decades, likely due to frequent use of cervical ultrasonography (US) and US-guided fine needle aspiration biopsy (FNA)., US is performed during follow-up after thyroidectomy, and US-guided FNA with cytology is used if suspicious cervical lymph nodes (LN) or thyroid bed masses are detected. Knowing that serum anti-Tg antibodies (sTgAb) affect the use of serum Tg (sTg) as a tumor marker, the aim of our study was to assess the usefulness of Tg determination in needle aspirates (FNA-Tg) in presence of sTgAb. This retrospective study included 149 patients with DTC and 159 aspirations of suspicious LN and thyroid bed masses. As expected, there was a negative correlation between sTg and sTgAb levels (p<0.05), while FNA-Tg levels had a positive correlation with FNA-TgAb levels (p<0.05). Furthermore, we found a positive correlation between sTg and FNA-Tg levels (p<0.05), but not between sTgAb and FNA-TgAb or sTgAb and FNA-Tg. In conclusion, these results show that FNA-Tg values were not affected by sTgAb and that FNA-Tg measurement were highly effective in detecting cervical DTC metastases. However, combined use with cytology is suggested for neck evaluation because cytology could reveal metastases from other tumor sites.

THE ENIGMA OF LEWY BODY DEMENTIA: A CASE REPORT.

Lewy body dementia is a progressive neurodegenerative disease and is considered to be the second most common cause of dementia in the elderly. Because of the complexity of clinical presentation, it is often misdiagnosed and mistaken for other dementias, which may result in administering inappropriate therapy, and thus worsening of the patient condition. We reviewed a case of a 71-year-old patient whose clinical presentation gradually occurred with complex visual hallucinations, atypical extrapyramidal motor symptoms, fluctuating cognitive impairments with delirious episodes, and oscillating syncope. Depressive mood, impaired daily functioning and sensitivity to antipsychotics were also noted. Extensive diagnostic workup was performed with neuropsychological testing and use of single-photon emission computerized tomography. Considering the clinical presentation and diagnostic procedures performed, the diagnosis of Lewy body dementia was set and pharmacotherapy was revised. We discuss the importance of taking overall clinical presentation and diagnostic treatment in consideration and applying appropriate therapy to slow down the progression of the disease and exacerbation of the patient's psychological functions.

Self-expandable metal stent for dysphagia caused by mediastinal masses in patients with lung cancer.

BACKGROUND AND STUDY AIMS: We intended to evaluate the role of self-expandable metal stents (SEMS) for palliation of malignant dysphagia in patients with lung cancer. PATIENTS AND METHODS: During the period between May 2015 and September 2017, 42 SEMS have been placed for malignant dysphagia in patients with lung cancer. Stents have been placed under combined fluoroscopic and endoscopic guidance. RESULTS: Data from 42 patient were analysed. 35 patients (83%) were males and the mean age was 68,4 years (range 52-80 y). In 26 patients (61%) cause of dysphagia was extraluminal mediastinal lymphadenopathy and in others direct tumour infiltration of the oesophagus. A tracheo-oesophageal fistula (TEF) was seen in 8 patients (19%). Most of the patients (32 patients; 76%) had stage 3 dysphagia (able to swallow liquids only) and the rest (10 patients; 24%) stage 4 (unable to swallow saliva). Thirty stents (71%) were partially covered and 12 (29%) were fully covered. Five (12%) stents have been placed across the oesophagogastric junction due to infiltration of the cardia. There were no immediate complications except for aspiration pneumonia in 3 (7%) and minor bleeding in 2 (5%) patients which resolved spontaneously. Dysphagia score improved in all patients to stage 1 (dysphagia with certain solid food in 16 patients-38%) or stage 2 (able to swallow semi solid in 26 patients-62%). In 3 (7%) patients during the follow-up we encountered tumour overgrowth and in 1 patients the TEF was not sealed so they have been referred for gastrostomy. No other long term complications were recorded. Most of the patients (30 patients- 71%) died during the follow-up, with mean survival of 4 months (range 2-9) after the stent placement. CONCLUSION: Placing SEMS in patients with lung cancer is safe and highly effective in relieving dysphagia with significant improvement in quality of life.