Highlights • Parkinson’s Disease Related Pattern (PDRP) is a robust metabolic biomarker of PD. • PDRP expression is reproducible across FDG-PET reconstruction algorithms (RA). • Different RA may ...shift PDRP expression but do not affect disease discrimination.
Background. Incidental
F-FDG uptake in the thyroid on PET-CT examinations represents a diagnostic challenge. The maximal standardized uptake value (SUV
) is one possible parameter that can help in ...distinguishing between benign and malignant thyroid PET lesions.
Patients and methods. We retrospectively evaluated
F-FDG PET-CT examinations of 5,911 patients performed at two different medical centres from 2010 to 2011. If pathologically increased activity was accidentally detected in the thyroid, the SUV
of the thyroid lesion was calculated. Patients with incidental
F-FDG uptake in the thyroid were instructed to visit a thyroidologist, who performed further investigation including fine needle aspiration cytology (FNAC) if needed. Lesions deemed suspicious after FNAC were referred for surgery.
Results. Incidental
F-FDG uptake in the thyroid was found in 3.89% ― in 230 out of 5,911 patients investigated on PET-CT. Malignant thyroid lesions (represented with focal thyroid uptake) were detected in 10 of 66 patients (in 15.2%). In the first medical centre the SUV
of 36 benign lesions was 5.6 ± 2.8 compared to 15.8 ± 9.2 of 5 malignant lesions (p < 0.001). In the second centre the SUV
of 20 benign lesions was 3.7 ± 2.2 compared to 5.1 ± 2.3 of 5 malignant lesions (p = 0.217). All 29 further investigated diffuse thyroid lesions were benign.
Conclusions. Incidental
F-FDG uptake in the thyroid was found in 3.89% of patients who had a PET-CT examination. Only focal thyroid uptake represented a malignant lesion in our study ― in 15.2% of all focal thyroid lesions. SUV
should only serve as one of several parameters that alert the clinician on the possibility of thyroid malignancy.
Nevrodegenerativne bolezni možganov, ki se klinično izrazijo kot demenca ali parkinsonizem, postajajo s staranjem prebivalstva vse pogostejše. Zgodnja in pravilna diagnoza je pomembna zaradi ...izključevanja ozdravljivih vzrokov, ustreznega simptomatskega zdravljenja, socialnih ukrepov in vključevanja bolnikov v klinične raziskave. Dokončno diagnozo večine nevrodegenerativnih bolezni možganov lahko postavimo le na podlagi patohistološkega vzorca možganovine. Za živa so nam v veliko pomoč funkcijske nuklearnomedicinske preiskave, s katerimi lahko prikažemo spremenjeno regionalno presnovo možganov, motnje na nivoju nevrotransmiterskih sistemov in patomorfološki substrat bolezni – kopičenje patoloških beljakovin. Glede na značilne spremembe regionalne presnove možganov, ki jih preučujemo s pozitronsko emisijsko tomografijo (PET) možganov z uporabo z radioaktivnim fluorom (18F) označene deoksiglukoze, lahko razlikujemo med alzheimerjevo boleznijo, demenco z lewyjevimi telesci, frontotemporalno demenco in redkejšimi vzroki kognitivnega upada ter med parkinsonovo boleznijo in drugimi nevrodegenerativnimi parkinsonizmi. Z ugotavljanjem integritete dopaminergičnega sistema (npr. scintigrafijo dopaminskega prenašalca; DaTSCAN) lahko razlikujemo med nevrodegenerativnimi parkinsonizmi in drugimi možnimi vzroki težav. Amiloidni PET možganov nam prikaže prisotnost in značilno razporeditev prekomernega kopičenja amiloida pri bolnikih z alzheimerjevo boleznijo že pred pojavom kliničnih znakov bolezni. V prispevku predstavljamo nuklearno medicinske preiskave, obravnavamo indikacije in značilne spremembe ter omejitve teh preiskav v diagnostiki nevrodegenerativnih bolezni možganov.
Dear Editor, We investigated the clinical outcome of treating castration-resistant prostate cancer (CRPC) patients with autologous immunohybridoma cell (aHyC) vaccine generated by electrofusing ...autologous dendritic (DC) and tumor cells (TC), and tested whether the immunological response, involving the CD56brightCD16− natural killer (NK), putative pro-metastatic cells,1,2 correlates with survival of CRPC patients. DCs are able to activate both naive and memory T cells, ideally suited for augmenting antitumor immune responses.4 Consistent with this, vaccination with enriched blood-derived DCs loaded with three tumor-associated antigens resulted in more frequent detection of antigen-specific T cells in CRPC patients.5 Here, whole TCs were electrofused with DCs to produce aHyC vaccine.6 The advantage of such hybridomas is their capacity of presenting both known and yet unknown tumor-associated antigens to T-lymphocytes. Human NK lymphocytes are involved in antitumor immunity, and CD56brightCD16− NK cells are considered immunoregulatory cytokine-producing cells, representing 5%–10% of all NK cells in peripheral blood.9 The levels of counterpart CD56dimCD16+ NK cells were unaltered compared to baseline in both groups. ...a negative correlation between the abundance of CD56brightCD16− NK cells and OS in melanoma patients was observed.10 In conclusion, these results indicate that aHyC treatment attenuates an increase in CD56brightCD16− NK cell subpopulation in peripheral blood, benefiting CRPC patient survival.
Priporočila za obravnavo bolnikov z limfedemom Planinšek Ručigaj, Tanja; Kozak, Matija; Slana, Ana ...
Zdravniški vestnik (Ljubljana, Slovenia : 1992),
09/2018, Letnik:
87, Številka:
7-8
Journal Article
Recenzirano
Odprti dostop
V prispevku so predstavljena priporočila za obravnavo bolnikov z limfedemom. Prikazana je klinična slika, diagnosticiranje in različni načini obravnave.
Purpose
Differentiation among parkinsonian syndromes may be clinically challenging, especially at early disease stages. In this study, we used
18
F-FDG-PET brain imaging combined with an automated ...image classification algorithm to classify parkinsonian patients as Parkinson’s disease (PD) or as an atypical parkinsonian syndrome (APS) at the time when the clinical diagnosis was still uncertain. In addition to validating the algorithm, we assessed its utility in a “real-life” clinical setting.
Methods
One hundred thirty-seven parkinsonian patients with uncertain clinical diagnosis underwent
18
F-FDG-PET and were classified using an automated image-based algorithm. For 66 patients in cohort A, the algorithm-based diagnoses were compared with their final clinical diagnoses, which were the gold standard for cohort A and were made 2.2 ± 1.1 years (mean ± SD) later by a movement disorder specialist. Seventy-one patients in cohort B were diagnosed by general neurologists, not strictly following diagnostic criteria, 2.5 ± 1.6 years after imaging. The clinical diagnoses were compared with the algorithm-based ones, which were considered the gold standard for cohort B.
Results
Image-based automated classification of cohort A resulted in 86.0% sensitivity, 92.3% specificity, 97.4% positive predictive value (PPV), and 66.7% negative predictive value (NPV) for PD, and 84.6% sensitivity, 97.7% specificity, 91.7% PPV, and 95.5% NPV for APS. In cohort B, general neurologists achieved 94.7% sensitivity, 83.3% specificity, 81.8% PPV, and 95.2% NPV for PD, while 88.2%, 76.9%, 71.4%, and 90.9% for APS.
Conclusion
The image-based algorithm had a high specificity and the predictive values in classifying patients before a final clinical diagnosis was reached by a specialist. Our data suggest that it may improve the diagnostic accuracy by 10–15% in PD and 20% in APS when a movement disorder specialist is not easily available.
Purpose
The purpose of this study was to identify the specific metabolic brain pattern characteristic for Parkinson’s disease (PD): Parkinson’s disease-related pattern (PDRP), using network analysis ...of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) brain images in a cohort of Slovenian PD patients.
Methods
Twenty PD patients (age 70.1 ± 7.8 years, Movement Disorder Society Unified Parkinson’s Disease Motor Rating Scale (MDS-UPDRS-III) 38.3 ± 12.2; disease duration 4.3 ± 4.1 years) and 20 age-matched normal controls (NCs) underwent FDG-PET brain imaging. An automatic voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was applied to these scans for PDRP-Slovenia identification.
Results
The pattern was characterized by relative hypermetabolism in pallidum, putamen, thalamus, brain stem, and cerebellum associated with hypometabolism in sensorimotor cortex, posterior parietal, occipital, and frontal cortices. The expression of PDRP-Slovenia discriminated PD patients from NCs (
p
< 0.0001) and correlated positively with patients’ clinical score (MDS-UPDRS-III,
p
= 0.03). Additionally, its topography agrees well with the original PDRP (
p
< 0.001) identified in American cohort of PD patients. We validated the PDRP-Slovenia expression on additional FDG-PET scans of 20 PD patients, 20 NCs, and 25 patients with atypical parkinsonism (AP). We confirmed that the expression of PDRP-Slovenia manifests good diagnostic accuracy with specificity and sensitivity of 85–90% at optimal pattern expression cutoff for discrimination of PD patients and NCs and is not expressed in AP.
Conclusion
PDRP-Slovenia proves to be a robust and reproducible functional imaging biomarker independent of patient population. It accurately differentiates PD patients from NCs and AP and correlates well with the clinical measure of PD progression.
Among attempts to delay development of resistance to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) with activating mutations of epidermal growth ...factor receptor (EGFR), intercalated therapy has not been properly evaluated. In a phase II trial, 38 patients with EGFR mutated NSCLC in advanced stage were treated with 4 to 6 3-weekly cycles of intercalated schedule with gemcitabine (1250 mg/m2, days 1 and 4), cisplatin (75 mg/m2, day 2) and erlotinib (150 mg, days 5 - 15), followed by continuous erlotinib as maintenance. In addition to standard radiologic evaluation according to RECIST, PET/CT was done prior to treatment and at 6 months, using PERCIST as a method for assessment of response. The primary endpoint was progression-free survival (PFS). In general, tolerance to treatment was good, even among 8 patients with performance status 2-3 and 13 patients with brain metastases; grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. Complete response (CR) or partial response (PR) were seen in 15 (39.5%) and 17 (44.7%) cases, respectively. All cases of CR were confirmed also by PET/CT. Median PFS was 23.4 months and median overall survival (OS) was 38.3 months. After a median follow-up of 35 months, 8 patients are still in CR and on maintenance erlotinib. In conclusion, intercalated treatment for treatment-naive patients with EGFR activating mutations leads to excellent response rate and prolonged PFS and survival. Comparison of the intercalated schedule to monotherapy with TKIs in a randomized trial is warranted.
Background
Alzheimer’s disease (AD) is marked by accumulation of Aβ and tau protein causing neurodegeneration in the brain. AD represents a pathological and clinical continuum, ranging from mild ...cognitive impairment (MCI) to dementia. A specific metabolic imaging biomarker of AD ‐ Alzheimer’s disease‐related pattern (ADRP) has been previously identified from 2‐18Ffluorodeoxyglucose positron emission tomography (2‐18FFDG‐PET) scans of clinically diagnosed AD patients, using scaled subprofile model based on principal component analysis (SSM/PCA) 1–3. However the clinical diagnosis may be wrong in substantial number of cases 4. We aimed to identify ADRP on patients with Alzheimer’s pathological changes in cerebrospinal (CSF) fluid and to validate it in an independent group of AD and other dementia patients and compare it to the original ADRP 1.
Method
2‐18FFDG‐PET scans from 20 AD1 and 20 normal controls (NC1) were used for pattern identification. Additional 110 scans were analyzed for validation: 68 from AD patients (37 AD2, 13 atypical clinical presentation AD (atAD), 18 MCI), 21 with frontotemporal dementia (FTD), 8 non‐AD MCI and 13 NC2 (Table 1). AD was defined with CSF biomarkers as: Aβ42 < 815 pg/ml, pTau > 60 pg/ml, tTau > 400 pg/ml. Topographic profile rating algorithm was used to prospectively calculate ADRP Z‐scores from subjects scans3. Mini‐mental state examination (MMSE) was performed in all patients.
Results
ADRP was identified and voxel weights were found to be stable by bootstrap resampling, Figure 1. Pattern’s expression was significantly higher in AD1 than NC1 (p<0.001) and it strongly correlated (r=‐0.70) with MMSE. Pattern’s expression was also higher in AD2 than NC2 (p<0.001), MCI vs. NC2 (p<0.001), MCI vs. non‐AD MCI (p=0.02) and AD2 vs. FTD (p=0.02), Figure 2. Newly identified pattern moderately correlated (r=0.52) with the original one 1.
Conclusions
We identified ADRP on a cohort of pathologically confirmed AD patients, which was not done before. ADRP has shown to be a reliable metabolic biomarker of AD related neurodegeneration. References: (1) Mattis,PJ. et al. Neurology 87,1925–33(2016); (2) Teune,LK. et al. Curr Alzheimer Res 11,725–32(2014); (3) Spetsieris,PG. & Eidelberg,D. Neuroimage 54,2899–914(2011); (4) Beach,TG. et al. J. Neuropathol. Exp. Neurol. 71,266–273(2012).
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