Východiska: Adenomatóza jater je velmi vzácné onemocnění. V literatuře se nám podařilo najít pouze dvě kazuistiky dokumentující obraz tohoto onemocnění na PET/CT s 18F-fludeoxyglukózou (FDG-PET/CT). Případ: U 52leté pacientky s necharakteristickými bolestmi v epigastriu bez onkologické anamnézy s negativními onkomarkery a bez klinických známek generalizované neoplazie byla při sonografii zachycena četná jaterní ložiska. Doplněné MR vyšetření vyjádřilo podezření na metastatický původ ložisek a bylo indikováno FDG-PET/CT s cílem identifikovat primární tumor a posoudit rozsah onemocnění. Při celotělovém FDG-PET/CT vyšetření se v játrech zobrazila mnohočetná (> 20) výrazně hypermetabolická ložiska velikosti 3–20 mm v průměru dosahující relativní akumulace SUVBWmax = 13 spolu s několika ametabolickými cystami; jinde v rozsahu vyšetření ložiskově patologicky zvýšená metabolická aktivita nebyla patrná. Následně pacientka podstoupila biopsii cílenou na jedno z hypermetabolických jaterních ložisek s nálezem HNF 1A inaktivované varianty hepatocelulárního adenomu; maligní primární ani sekundární bujení nebylo prokázáno. S ohledem na histologický nález a velký počet jaterních ložisek byla jako konečná diagnóza stanovena adenomatóza jater. Pacientka zůstává v trvalém sledování. Závěr: Adenomatózní ložiska byla při FDG-PET/CT vyšetření výrazně hypermetabolická a touto metodou je nebylo možno odlišit od nádorových metastáz. Náš nález je v souladu s dalšími dvěma pozorováními, která se nám podařilo dohledat v literatuře.
Background: Liver adenomatosis is a very rare disease. In the literature, we were able to find only two case reports documenting the appearance of this disease on PET/CT with 18F-fludeoxyglucose (FDG-PET/CT). Case: Numerous liver foci were detected during sonography in a 52-year-old female patient with uncharacteristic pain in the epigastrium without oncological history, with negative oncomarkers and without clinical signs of generalized neoplasia. Complementary MRI examination expressed the suspicion of metastatic origin of the foci, and FDG-PET/CT was indicated in order to identify the primary tumour and assess the extent of the disease. A whole-body FDG-PET/CT examination showed multiple (> 20) markedly hypermetabolic liver foci with 3–20 mm in diameter, reaching a relative accumulation of SUVBWmax = 13, together with several ametabolic cysts; elsewhere in the scope of the examination, focally pathologically increased metabolic activity was not evident. Subsequently, the patient underwent a biopsy targeted at one of the hypermetabolic liver foci with the finding of HNF 1A inactivated variant of hepatocellular adenoma; primary or secondary malignancy was not demonstrated. Considering the histological findings and the large number of liver foci, the final diagnosis of liver adenomatosis was set. The patient remains under continuous observation. Conclusion: Adenomatous foci were markedly hypermetabolic during FDG-PET/CT examination and could not be distinguished from tumour metastases by this method. Our finding is consistent with two other observations we were able to find in the literature.
- Klíčová slova
- adenomatóza,
- MeSH
- hepatocelulární karcinom diagnóza MeSH
- játra * diagnostické zobrazování patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- PET/CT metody MeSH
- pozitronová emisní tomografie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
AIM: Our study aimed to evaluate the use of positron emission tomography/computed tomography (PET/CT) in the initial staging of head and neck squamous cell carcinoma (HNSCC), including assessment of local and distant spread of the disease. We also aimed to compare the accuracy of PET/CT in the evaluation of human papillomavirus (HPV) positive and HPV-negative oropharyngeal carcinoma. MATERIAL AND METHODS: This single-center, prospective study was conducted between August 2016 and September 2021. A total of 198 patients with HNSCC who underwent PET/CT within the primary staging were included. We compared PET/CT results with histological findings. We calculated the accuracy, sensitivity, specificity, and positive and negative predictive values to assess the primary tumor, cervical lymph nodes, and distant metastases. RESULTS: PET/CT showed a high success rate (32%) in revealing the primary site of carcinoma of unknown primary (CUP). The accuracy of PET/CT in displaying the primary tumor, cervical lymph node metastases, and distant metastases was 89.4%, 85.4%, and 87.4%, respectively. The method provided high sensitivity but lower specificity in all three areas. Specifically, PET/CT showed low specificity in the assessment of small tumors (75%), metastatic involvement of cervical lymph nodes (69.6%), and HPV-positive oropharyngeal carcinoma (55.6%). CONCLUSIONS: The high accuracy of PET/CT to identify distant metastases and whole-body staging in one diagnostic step accelerated primary staging and resulted in earlier commencement of therapy. However, it also led to an overestimation of clinical findings and thus to extensive surgical treatment, especially in patients with small tumors, metastatic involvement of cervical lymph nodes, and HPV- positive oropharyngeal carcinoma. PET/CT is also useful for CUP diagnostics.
- MeSH
- dlaždicobuněčné karcinomy hlavy a krku diagnostické zobrazování MeSH
- infekce papilomavirem * MeSH
- lidé MeSH
- lymfatické uzliny diagnostické zobrazování MeSH
- nádory hlavy a krku * diagnostické zobrazování MeSH
- nádory orofaryngu * diagnostické zobrazování MeSH
- PET/CT MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: We investigated whether the reproducibility of standard visual reporting (STD method) in flutemetamol (FMM) PET can be improved using a newly introduced method that uses grey matter edges derived from the perfusion phase (GM-EDGE method). METHODS: Two-phase FMM PET was performed in 121 patients with mild cognitive impairment. Five nuclear medicine physicians blindly and independently evaluated all late-phase scans, initially employing the STD method and later the GM-EDGE method. A five-point scale was used to express the degree of amyloid positivity, and a binary classification (positive/negative) was used in combination with subjective confidence (five-point scale). Multirater Fleiss' kappa, intraclass correlation coefficient (ICC) and inter-rater reliability (Cohen's kappa) were determined for the STD and GM-EDGE methods. RESULTS: The weighted Cohen's kappa values for the five-point measure of amyloid positivity ranged from 0.63 to 0.73 (median 0.70) for the STD method and from 0.76 to 0.89 (median 0.80) for the GM-EDGE method (ICC 0.84, 95% CI 0.79-0.88, for the STD method; 0.91, 95% CI 0.89-0.94, for the GM-EDGE method). The nonweighted Cohen's kappa value for the binary classification ranged from 0.73 to 0.93 (median 0.82) for the STD method and 0.90 to 0.97 (median 0.93) for the GM-EDGE method (Fleiss' kappa 0.82, 95% CI 0.77-0.88, for the STD method; 0.93, 95% CI 0.87-0.99, for the GM-EDGE method). The GM-EDGE method resulted in significantly greater subjective confidence in the readings of four physicians (p < 0.010). The binary classification was concordant among all five physicians in 80.8% of the scans using the STD method and in 91.6% of the scans using the GM-EDGE method (p = 0.016). CONCLUSION: The newly introduced GM-EDGE method was associated with significantly higher inter-rater agreement among physicians and higher subjective confidence in the reading. The method is easy to implement in clinical practice, especially when the perfusion phase is utilized clinically.
- MeSH
- amyloidní beta-protein metabolismus MeSH
- dospělí MeSH
- kognitivní dysfunkce diagnostické zobrazování metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- PET/CT * MeSH
- počítačové zpracování obrazu * MeSH
- šedá hmota diagnostické zobrazování metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Through high-throughput next-generation sequencing of promoters of solute carrier and ATP-binding cassette genes, which encode drug transporters, we aimed to identify SNPs associated with the response to imatinib administered for first-line treatment of patients with chronic myeloid leukemia. METHODS: In silico analysis using publicly available databases was done to select the SLC and ABC genes and their promoters for the next-generation sequencing. SNPs associated with the imatinib response were identified using Fisher's exact probability tests and subjected to the linkage disequilibrium analyses with regulatory loci of concerned genes. We analyzed cumulative achievement of major molecular response and probability of event free survival in relation to identified SNP genotypes in 129 CML patients and performed multivariate analysis for determination of genotypes as independent predictors of outcome. Gene expression analysis of eight cell lines naturally carrying different genotypes was performed to outline an impact of genotypes on the gene expression. RESULTS: We observed significant differences in the frequencies of the rs460089-GC and rs460089-GG (SLC22A4) genotypes among rs2631365-TC (SLC22A5) genotype carriers that were associated with optimal and non-optimal responses, respectively. Loci rs460089 and rs2631365 were in highly significant linkage disequilibrium with 12 regulatory loci in introns of SLC22A4 and SLC22A5 encoding imatinib transporters. Genotype association analysis with the response to imatinib indicated that rs460089-GC carriers had a significantly higher probability of achieving a stable major molecular response (BCR-ABL1 transcript level below or equal to 0.1% in the international scale). In contrast, the rs460089-GG represented a risk factor for imatinib failure, which was significantly higher in rs460089-GG_rs2631365-TC carriers. CONCLUSIONS: This exploratory study depicted potentially important genetic markers predicting outcome of imatinib treatment, which may be helpful for tailoring therapy in clinical practice.
- MeSH
- buňky K562 MeSH
- chronická myeloidní leukemie farmakoterapie genetika MeSH
- genotyp MeSH
- imatinib mesylát aplikace a dávkování terapeutické užití MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- mutační rychlost MeSH
- nádorové buněčné linie MeSH
- promotorové oblasti (genetika) MeSH
- proteiny přenášející organické kationty genetika MeSH
- protinádorové látky aplikace a dávkování terapeutické užití MeSH
- rodina nosičů rozpuštěných látek 22, člen 5 genetika MeSH
- sekvenční analýza DNA metody MeSH
- vazebná nerovnováha MeSH
- výsledek terapie MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: It is generally accepted that a non-fasting state reduces [18F]FDG-PET quality, but the significance of higher levels of fasting blood glucose has aroused some doubts over time. The aim of this work was to provide further evidence to clarify this issue and its impact on the handling of hyperglycemic patients in daily routine. METHODS: Muscle and liver standardized uptake values (SUV) and their ratio, tumor SUV and the frequency of positive PET findings were retrospectively analyzed in 116 hyperglycemic (HG) patients (>11 mmol/L), in 116 patients with slightly elevated glycemia (SEG) (5.6-7.0 mmol/L) and in 116 normoglycemic (NG) patients (4.7 mmol/L). RESULTS: No significant difference was found in the muscle to liver ratio, in muscle SUV and in the frequency of positive PET findings among HG, SEG and NG patients. HG patients exhibited ~10% higher liver SUV in comparison to SEG and NG patients; a positive correlation (r=0.2849) was found between liver SUV and blood glucose levels. Significantly higher tumor SUV was present in SEG patients. CONCLUSIONS: We did not confirm that hyperglycemia in a fasting state negatively influences the diagnostic quality of [18F]FDG-PET. The positive correlation between liver SUV and blood glucose levels is clinically negligible and might be explained by increased fasting hepatic gluconeogenesis in diabetics. Our data encourage the performance of [18F]FDG-PET investigations under fasting conditions, regardless of the mild to medium elevation of fasting blood glucose level.
- MeSH
- fluorodeoxyglukosa F18 * MeSH
- hyperglykemie diagnostické zobrazování metabolismus MeSH
- játra diagnostické zobrazování metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- omezení příjmu potravy * metabolismus MeSH
- pozitronová emisní tomografie metody MeSH
- retrospektivní studie MeSH
- svaly diagnostické zobrazování metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
PURPOSE: Here, we studied whether amplicon next-generation deep sequencing (NGS) could improve the detection of emerging BCR-ABL1 kinase domain mutations in chronic phase chronic myeloid leukemia (CML) patients under tyrosine kinase inhibitor (TKI) treatment and discussed the clinical relevance of such sensitive mutational detection. METHODS: For NGS data evaluation including extraction of biologically relevant low-level variants from background error noise, we established and applied a robust and versatile bioinformatics approach. RESULTS: Results from a retrospective longitudinal analysis of 135 samples of 15 CML patients showed that NGS could have revealed emerging resistant mutants 2-11 months earlier than conventional sequencing. Interestingly, in cases who later failed first-line imatinib treatment, NGS revealed that TKI-resistant mutations were already detectable at the time of major or deeper molecular response. Identification of emerging mutations by NGS was mirrored by BCR-ABL1 transcript level expressed either fluctuations around 0.1 %(IS) or by slight transcript level increase. NGS also allowed tracing mutations that emerged during second-line TKI therapy back to the time of switchover. Compound mutants could be detected in three cases, but were not found to outcompete single mutants. CONCLUSIONS: This work points out, that next-generation deep sequencing, coupled with a robust bioinformatics approach for mutation calling, may be just in place to ensure reliable detection of emerging BCR-ABL1 mutations, allowing early therapy switch and selection of the most appropriate therapy. Further, prospective assessment of how to best integrate NGS in the molecular monitoring and clinical decision algorithms is warranted.
- MeSH
- bcr-abl fúzní proteiny genetika MeSH
- benzamidy terapeutické užití MeSH
- chronická myeloidní leukemie farmakoterapie genetika MeSH
- dospělí MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- mutace účinky léků MeSH
- piperaziny terapeutické užití MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- protinádorové látky terapeutické užití MeSH
- pyrimidiny terapeutické užití MeSH
- retrospektivní studie MeSH
- senioři MeSH
- tyrosinkinasy antagonisté a inhibitory MeSH
- výpočetní biologie MeSH
- vysoce účinné nukleotidové sekvenování * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In chronic myeloid leukemia, the identification of individual BCR-ABL1 fusions is required for the development of personalized medicine approach for minimal residual disease monitoring at the DNA level. Next generation sequencing (NGS) of amplicons larger than 1000 bp simplified and accelerated a process of characterization of patient-specific BCR-ABL1 genomic fusions. NGS of large regions upstream and downstream the individual breakpoints in BCR and ABL1 genes, respectively, also provided information about the sequence variants such are single nucleotide polymorphisms.
