Článek se zabývá problematikou personalizované léčby akromegalie s důrazem na predikci terapeutické odpovědi. V kontextu rychle se rozvíjející oblasti personalizované medicíny zdůrazňuje variabilitu klinických, biochemických a radiologických rysů akromegalie a potřebu přesnější klasifikace a personalizovaných terapeutických přístupů. Chirurgie zůstává hlavním terapeutickým přístupem a v článku jsou analyzovány předoperační prediktory úspěšné operace, jako jsou vyšší koncentrace růstového hormonu před zákrokem a negativní vliv invaze kavernózního sinu. Při terapii somatostatinovými analogy jsou zkoumány faktory, včetně intenzity signálu na MRI a exprese receptorů SSTR2A a SSTR5. Dále je diskutován význam matematických analýz a modelů umělé inteligence při předpovědi terapeutické odpovědi. V současné době je nezbytné vyvinout nové algoritmy pro výběr terapie, aby bylo možné léčit pacienty s akromegalií efektivněji.
The article deals with the issue of personalized treatment of acromegaly with emphasis on prediction of therapeutic response. In the context of the rapidly developing field of personalized medicine, it emphasizes the variability of the clinical, biochemical and radiological features of acromegaly and the need for more accurate classification and personalized therapeutic approaches. Surgery remains the main therapeutic approach, and this article analyzes preoperative predictors of successful surgery, such as higher growth hormone concentrations before surgery and the negative impact of cavernous sinus invasion. Factors including signal intensity on MRI and SSTR2A and SSTR5 receptor expression are investigated during somatostatin analogue therapy. The importance of mathematical analyses and artificial intelligence models in predicting therapeutic response is also discussed. Currently, it is necessary to develop new algorithms for therapy selection in order to treat patients with acromegaly more effectively.
- MeSH
- akromegalie * terapie MeSH
- individualizovaná medicína MeSH
- lidé MeSH
- neurochirurgické výkony MeSH
- somatostatin analogy a deriváty farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
OBJECTIVES: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by increased platelet destruction and altered production. Despite the well-described pathophysiological background of immune dysregulation, current treatment guidelines consist of monotherapy with different drugs, with no tool to predict which patient is more suitable for each therapeutic modality. METHODS: In our study, we attempted to determine differences in the immune setting, comparing the patients' responses to administered therapy. During 12-month follow-up, we assessed blood count, antiplatelet autoantibodies, and T lymphocyte subsets in peripheral blood in 35 patients with ITP (newly diagnosed or relapsed disease). RESULTS: Our data show that the value of antiplatelet autoantibodies, the percentage of cytotoxic T lymphocytes, and the immunoregulatory index (IRI, CD4+ / CD8+ T cell ratio) differ significantly by treatment response. Responders have a higher IRI (median 2.1 vs. 1.5 in non-responders, P = 0.04), higher antiplatelet autoantibodies (median 58 vs. 20% in non-responders, P = 0.01) and lower relative CD8+ T cells count (P = 0.02) before treatment. DISCUSSION: The results suggest that immunological parameters (antiplatelet autoantibodies, relative CD8+ T cell count and IRI) could be used as prognostic tools for a worse clinical outcome in patients with ITP. CONCLUSION: These biomarkers could be utilized for stratification and eventually selection of treatment preferring combination therapy.
- MeSH
- autoprotilátky MeSH
- CD8-pozitivní T-lymfocyty MeSH
- idiopatická trombocytopenická purpura * diagnóza farmakoterapie MeSH
- lidé MeSH
- lymfocyty MeSH
- trombocytopenie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cauda equina neuroendocrine tumors (CENETs) are neoplasms of uncertain histogenesis with overlapping features between those of paragangliomas (PGs) and visceral neuroendocrine tumors (NETs). We have explored their biological relationship to both subsets of neuroendocrine neoplasms. The clinical and radiological features of a cohort of 23 CENETs were analyzed. A total of 21 cases were included in tissue microarrays, along with a control group of 38 PGs and 83 NETs. An extensive panel of antibodies was used to assess epithelial phenotype (cytokeratins, E-cadherin, EpCAM, Claudin-4, EMA, CD138), neuronal and neuroendocrine features (synaptophysin, chromogranin A, INSM1, neurofilaments, NeuN, internexin-α, calretinin), chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase), and possible histogenesis (Sox2, T-brachyury, Oct3/4, Sox10). The cohort included 5 women (22%) and 18 men (78%). The average age at the time of surgery was 48.3 years (range from 21 to 80 years). The average diameter of the tumors was 39.27 mm, and invasion of surrounding structures was observed in 6/21 (29%) tumors. Follow-up was available in 16 patients (median 46.5 months). One tumor recurred after 19 months. No metastatic behavior and no endocrine activity were observed. Compared to control groups, CENETs lacked expression of epithelial adhesion molecules (EpCAM, CD138, E-cadherin, Claudin-4), and at the same time, they lacked features of chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase). We observed no loss of SDHB. Cytokeratin expression was present in all CENETs. All the CENETs showed variable cytoplasmic expression of T-brachyury and limited nuclear expression of Sox2. These findings support the unique nature of the neoplasm with respect to NETs and PGs.
- MeSH
- adhezní molekula epiteliálních buněk MeSH
- cauda equina * metabolismus patologie chirurgie MeSH
- claudin-4 MeSH
- lidé MeSH
- lokální recidiva nádoru patologie MeSH
- nádory centrálního nervového systému * patologie MeSH
- neuroendokrinní nádory * patologie MeSH
- paragangliom * MeSH
- represorové proteiny MeSH
- transkripční faktory MeSH
- tyrosin-3-monooxygenasa MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Subklinická hypotyreóza je poměrně častým jevem, zejména u starších pacientů. Je definována zvýšeným TSH spolu s normálními hladinami volných hormonů štítné žlázy. Oproti klinicky vyjádřené hypotyreóze jsou její rizika podstatně menší, a proto je klíčové vybrat pacienty, u kterých potencionální benefit léčby převáží její nežádoucí účinky. K tomu je třeba vzít v potaz věk pacienta, komorbidity, příznaky a míru elevace TSH. Léčba spočívá v substituci levothyroxinem s šetrnou titrací dávky vedoucí k normalizaci TSH. Neléčení pacienti by měli být sledováni v závislosti na rizikových faktorech, zejména pak na riziku progrese do klinicky vyjádřené hypotyreózy. Přístup ke každému pacientovi by měl být vždy individuální a flexibilní.
Subclinical hypothyroidism is a relatively common condition characterized by elevated serum TSH levels, but normal free thyroxine levels. The risks associated with subclinical hypothyroidism are less severe compared to those with overt hypothyroidism, making it essential to carefully select patients who would benefit from the treatment. Factors such as the patient ́s age, comorbidities, symptoms, and TSH concentration need to be considered in this selections proces. The therapy, if required, consists of levothyroxine substitution with carefull dose titration to avoid overtreatment. The goal is to normalize TSH levels. Untreated patients should be folowed up accordingly to their risk factors mainly the risk of progression to overt hypothyroidism. Aproach to each patient should be individulized and flexible.
- MeSH
- hormony štítné žlázy krev MeSH
- hypotyreóza * diagnóza farmakoterapie komplikace MeSH
- lidé MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- testy funkce štítné žlázy MeSH
- thyreotropin krev MeSH
- thyroxin aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Terapie levothyroxinem je součástí léčby diferencovaného karcinomu štítné žlázy již po desetiletí. Levothyroxin je podáván pacientům po totální tyreoidektomii (s nebo bez následné aplikace radiojodu) nejen k navození eutyreózy, ale také k potlačení produkce thyreotropního hormonu (TSH), protože TSH je považován za růstový faktor pro folikulární buňky štítné žlázy. Hlavní nevýhodou této léčby jsou známá rizika spojená s iatrogenně navozenou subklinickou či až klinickou hypertyreózou. Proto je nezbytný individuální přístup s porovnáním rizika rekurence onemocnění a rizika nežádoucích účinků supresní terapie v korelaci s komorbiditami a celkovým stavem pacienta. Časté a důsledné sledování pacientů s adekvátní úpravou dávky levothyroxinu k udržení TSH v cílovém rozmezí dle doporučení Americké tyroidální asociace (ATA) je zcela klíčové.
Levothyroxine therapy in management of diferentiated thyroid carcinoma (DTC) has been common practice for decades. Levothyroxine is being administered to patiens with DTC after total thyreoidectomy (with or without postopreative radioiodine treatment) not only to restore euthyroidism but to suppress the production of thyroid-stimulating hormone (TSH) as well because TSH is considered as a growth factor for thyroid follicular cells. However there has been a downside to this threatment recently. The main concerns are the known risks related to iatrogenic subclinical or even mild but clinicaly overt iatrogenic hyperthyroidism. Therefore individualized treatment approach aiming to balance between the risk of tumor recurence and the risks related to hypertyhroidism in view of pateints age, risk factors and comorbidities is essential. Close folow-up is therefore necessary with frequent dose adjustments according to target TSH values published in American Thyroid Association guidelines.
- MeSH
- hormonální substituční terapie MeSH
- karcinom chirurgie farmakoterapie MeSH
- lidé MeSH
- nádory štítné žlázy * chirurgie farmakoterapie MeSH
- nežádoucí účinky léčiv MeSH
- rizikové faktory MeSH
- thyreotropin účinky léků MeSH
- thyroxin * aplikace a dávkování terapeutické užití MeSH
- tyreoidektomie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Phox2B is a transcription factor responsible for chromaffin cell phenotype. Although it is used routinely for diagnosis of neuroblastoma, previous reports concerning its utility in the diagnosis of neuroendocrine neoplasms have been conflicting. We assessed Phox2b immunoreactivity in different neuroendocrine neoplasms. Tissue microarrays or whole sections of 36 paragangliomas (PGs), 91 well-differentiated neuroendocrine tumours of different organs (WDNETs), 31 neuroendocrine carcinomas (NECs), and 6 olfactory neuroblastomas (ONBs) were stained with Phox2B antibody (EP312) and GATA3. The percentage of positive cells and intensity was analysed using H-score. Phox2B immunoreactivity was seen in 97.2% (35/36) PGs, 11% (10/91) WDNETs, 9.7% (3/31) NECs, and 16.7% (1/6) ONBs. PGs were significantly more often positive (p < 0.001, χ2) than other neuroendocrine tumours, showing highest H-score (mean 144.9, SD ± 75.1) and percentage of positive cells (median 81.3%, IQR 62.5-92.5%). Compared to Phox2B-positive WDNETs, PGs showed significantly higher H-score (median 145 vs 7.5, p < 0.001) and percentage of positive cells (median 82.5% vs 4.5%, p < 0.001). Phox2B positivity was 97.2% sensitive and 89% specific for the diagnosis of PG. GATA3 was 100% sensitive and 88% specific for the diagnosis of PG. When combined, any Phox2B/GATA3 coexpression was 97.1% sensitive and 99.1% specific for the diagnosis of paraganglioma. Widespread Phox2B immunoreactivity is a highly characteristic feature of PGs and it can be used as an additional marker in differential diagnosis of neuroendocrine tumours.
Pitx2 is a transcription factor responsible for establishment of the right-left axis and development of the gut and pituitary. In mouse embryos, Pitx2 is expressed in the greater curvature of the stomach and midgut. Previously, Pitx2 was studied in pituitary neuroendocrine tumours but not in other NETs. Pitx2 expression was immunohistochemically assessed in whole sections and tissue microarrays in a cohort of 224 neuroendocrine neoplasms, and was analysed in 29 cases. The cohort included 18 cauda equina NETs, 38 paragangliomas, 98 cases of primary visceral NETs from different organs, 23 metastases of visceral NETs and 47 neuroendocrine carcinomas (NECs). Pitx2 expression was observed in 29.5% (29 of 98) NETs and 14.9% (7 of 47) NECs, but was not observed in any paraganglioma or cauda equina NET. Pitx2 was observed only in tumours of midgut-derived organs, including the small intestine (100%, 20 of 20), appendix (88.9%, eight of nine) and large intestine (9.1%, one of 11 - only caecal NET). The NETs of remaining locations were negative. Pitx2 was 96.7% sensitive and 100% specific for NETs of midgut origin. In NECs, Pitx2 positivity was observed in goblet cell adenocarcinoma (75%, three of four), medullary thyroid carcinoma (42.9, three of seven) and one Merkel cell carcinoma (25%, one of four). In metastatic NETs, Pitx2 was observed in all the tumours originating in the small intestine (n = 17) or caecum (n = 1). No positivity was observed in tumours from other locations (four pancreas, one lung). We observed no correlation between immunoreactivity and mRNA expression. Thus, Pitx2 immunohistochemistry can be helpful in assessing the midgut origin of NETs.
Autoři prezentují případ netraumatického nádorového pravostranného chylothoraxu, který byl úspěšné léčen embolizací ductus thoracicus. Výkon byl proveden transabdominálně, antegrádním přístupem přes cisterna chyli zobrazenou pomocí intranodální lymfografie. K embolizaci byly použity mikrospirály a akrylátové tkáňové lepidlo. Nemocný je sledován 5 měsíců a je bez recidivy chylothoraxu.
The authors present a case of a patient with non-traumatic right-sided chylothorax which was successfully treated by thoracic duct embolization. The procedure was performed through the cisterna chyli which was visualised by intranodal lymphography. The coils and acrylic tissue glues were used for embolization. The patient has been followed for 5 months and is free of recurrence of chylothorax.
- MeSH
- adenokarcinom diagnóza komplikace terapie MeSH
- diagnostické techniky dýchacího ústrojí využití MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- komplikace diabetu diagnóza terapie MeSH
- lidé MeSH
- nádory plic diagnóza komplikace patofyziologie MeSH
- plicní fibróza diagnóza komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
