Androgen deprivation therapy has long been the first-line treatment for hormone-sensitive prostate cancer (HSPC). After progression to castration-resistant prostate cancer (CRPC), androgen receptor pathway inhibitors (ARPIs) are commonly used. Recently, combined therapy with androgen deprivation and an ARPI has been recommended for metastatic HSPC patients. Novel markers are urgently needed for monitoring this disease and for making therapeutic decisions. Plasma samples were collected from 140 patients with either metastatic HSPC (n = 72) or CRPC (n = 68) before the start of ARPI therapy. Digital PCR was used to assess AR gene amplification, while the expression levels of miR-375 were measured by quantitative PCR. Sixteen other clinical markers were also evaluated, including prostate-specific antigen (PSA), chromogranin A (CGA), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), C-reactive protein (CRP), lymphocyte-to-monocyte ratio, and platelet count. A multivariate analysis, adjusted for age and metastatic dissemination, identified miR-375 expression and lymphocyte-to-monocyte ratio to be the independent negative predictors of ARPI therapy failure in CRPC patients. Regarding the HSPC patients, this article reports the primary finding of the independent negative predictive value of platelet count, CRP, and CGA for the failure of combined androgen deprivation therapy and ARPI.

• MeSH
• Receptors, Androgen genetics   MeSH
• C-Reactive Protein * metabolism   MeSH
• Chromogranin A * blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• MicroRNAs * genetics   blood   MeSH
• Biomarkers, Tumor blood   MeSH
• Prostatic Neoplasms, Castration-Resistant * blood   genetics   pathology   drug therapy   diagnosis   MeSH
• Treatment Failure MeSH
• Prognosis MeSH
• Prostate-Specific Antigen * blood   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Blood Platelets * metabolism   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

To explore the mechanism whereby cGAS-STING pathway regulates the pyroptosis of cryptorchidism cells, with a view to finding a new strategy for clinically treating cryptorchidism-induced infertility. Spermatogonial GC-1 cells were heat stimulated to simulate the heat hurt microenvironment of cryptorchidism. The cell viability was assayed by CCK-8, and cellular DNA damage was detected by gamma-H2AX immunofluo-rescence assay. Flow cytometry was employed to assess pyroptosis index, while western blot, ELISA and PCR were used to examine the expressions of pyroptosis-related proteins (Caspase-1, IL-1beta, NLRP3) and cGAS-STING pathway proteins (cGAS, STING). After STING silencing by siRNA, the expressions of pyroptosis-related proteins were determined. Pyroptosis occurred after heat stimulation of cells. Morphological detection found cell swelling and karyopyknosis. According to the gamma-H2AX immunofluorescence (IFA) assay, the endonuclear green fluorescence was significantly enhanced, the gamma-H2AX content markedly increased, and the endonuclear DNA was damaged. Flow cytometry revealed a significant increase in pyroptosis index. Western blot and PCR assays showed that the expressions of intracellular pyrogenic proteins like Caspase-1, NLRP3 and GSDMD were elevated. The increased STING protein and gene expressions in cGAS-STING pathway suggested that the pathway was intracellularly activated. Silencing STING protein in cGAS-STING pathway led to significantly inhibited pyroptosis. These results indicate that cGAS-STING pathway plays an important role in heat stress-induced pyroptosis of spermatogonial cells. After heat stimulation of spermatogonial GC-1 cells, pyroptosis was induced and cGAS-STING pathway was activated. This study can further enrich and improve the molecular mechanism of cryptorchidism.

• MeSH
• Acetates * MeSH
• Chromogranin A MeSH
• Phenols * MeSH
• Caspase 1 MeSH
• Cryptorchidism * MeSH
• Humans MeSH
• Nucleotidyltransferases MeSH
• NLR Family, Pyrin Domain-Containing 3 Protein MeSH
• Pyroptosis MeSH
• Signal Transduction MeSH
• Spermatogonia MeSH
• Heat Stroke * MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH

V posledních letech roste incidence gastroenteropankreatických neuroendokrinních tumorů (GEP NET) a objevují se nové možnosti terapie těchto nádorů. Zavedenými metodami terapie tohoto onemocnění je chirurgická léčba, radioterapie a u méně diferencovaných typů chemoterapie, ke kompletní remisi onemocnění však dochází pouze asi u 5 % pacientů. V posledních třech letech byla proto v ČR zavedena nová terapeutická modalita nukleární medicíny – jedná se o (177 Lu)oxodotreotid, radiofarmakum vykazující vysokou afinitu vůči somatostatinovým receptorům typu 2 (SST2) zvýšeně exprimovaným maligními buňkami GEP NET. Článek podává základní souhrnné informace o peptidové receptorové radioterapii pomocí (177 Lu)oxodotreotidu (Lutathera).

In recent years, the incidence of gastroenteropancreatic neuroendocrine tumours (GEP- NETs) has been increasing, and new treatment options for these tumours are emerging. The established methods of therapy for this disease are surgical treatment, radiotherapy and, in less differentiated types, chemotherapy. However, complete remission of the disease only occurs in about 5% of patients. Therefore, in the last three years, a new therapeutic modality of nuclear medicine was introduced in the Czech Republic – it is (177Lu)oxodotreotide, a radiopharmaceutical showing a high affinity for somatostatin receptors type 2 (SST2) that are highly expressed by malignant GEP-NET cells. The article provides basic summary information about peptide receptor radiotherapy using (177 Lu)oxodotreotide (Lutathera).

• Keywords
• Lutathera, 68Ga-DOTATOC,
• MeSH
• Biomarkers analysis   blood   MeSH
• Chromogranin A analysis   MeSH
• Carcinoid Tumor * surgery   diagnosis   drug therapy   classification   MeSH
• Humans MeSH
• Pancreatic Polypeptide radiation effects   MeSH
• Positron Emission Tomography Computed Tomography methods   MeSH
• Radiotherapy * methods   MeSH
• Receptors, Peptide MeSH
• Receptors, Somatostatin drug effects   MeSH
• Risk Factors MeSH
• Insurance, Health, Reimbursement MeSH
• Check Tag
• Humans MeSH

Úvod: V našem příspěvku chceme připomenout vzácnou diagnózu. Kazuistika: 54letý pacient, obézní hypertonik a kuřák, byl 12 let ošetřován pro intermitentní bolesti břicha. První gastroskopii pro krvácející vřed absolvoval v r. 2010. V dalších letech následovaly opakované gastroskopie s proměnlivým postižením jícnu až duodena. Kapslová enteroskopie diagnostiku dále neposunula. Pacient několikrát podstoupil koloskopii a MR enterografii, jednoznačně patologický nález nepřinesly. V květnu 2022 byl přijat na naše oddělení pro bolesti břicha, zvracení. Tentokrát na gastroskopii byly patrné mnohočetné drobné ulcerace duodena a jejuna s koaguly, která činila mechanickou překážku. Pro podezření na gastrinom byl doplněn chromogranin A, který byl vysoký. Somatostatinový octreoscan byl však negativní. Až 68Ga-DOTATOC PET (pozititronová emisní tomografie s radiofarmakem DOTA, značeným galiem68) nalezl ložisko v podjaterní krajině, které ale nemělo žádný korelát na CT. Diagnózu jsme uzavřeli jako gastrinom s Zollinger-Ellisonovým syndromem. Endoskopicky se podařilo nalézt asi 1cm tumor duodena. Pacient v říjnu 2022 podstoupil excizi stěny duodena. Patolog potvrdil naši diagnózu gastrinomu. Závěr: Touto kazuistikou chceme připomenout, že i neuroendokrinní tumory musíme zařadit do našich diferenciálně diagnostických úvah. Současně chceme upozornit, že dle ESMO doporučení bychom měli k diagnostice preferenčně využívat 68Ga-DOTATOC PET/CT místo scintigrafického vyšetření (111In-Octreoscanu).

Introduction: In our text, we want to highlight a rare diagnosis. Case report: A 54-year-old obese, hypertensive male smoker had been investigated for intermittent abdominal pain for 12 years. The first gastroscopy for a bleeding ulcer was conducted in 2010. In the subsequent years, repeated gastroscopies revealed variable involvement from the esophagus to the duodenum. Capsule enteroscopy did not provide further specification of the diagnosis. The patient underwent colonoscopy and MRI enterography multiple times, with no unequivocal pathological findings. In May 2022, he was admitted to our department for abdominal pain and vomiting. This time, gastroscopy revealed multiple small ulcers in the duodenum and jejunum with clots causing a mechanical obstruction. Chromogranin A was elevated, raising suspicion of gastrinoma. However, somatostatin receptor-based imaging (Octreoscan) was negative. Only the 68Ga-DOTATOC PET (positron emission tomography with the radiopharmaceutical DOTA, labeled with gallium-68) identified a lesion in the subhepatic region, which had no correlation on CT. We concluded the diagnosis as gastrinoma with the Zollinger–Ellison syndrome. Endoscopically, a 1cm tumor was found in the duodenum. In October 2022, the patient underwent an excision of the duodenal wall, and the pathology assessment confirmed our diagnosis of gastrinoma. Conclusion: With this case report, we want to emphasize the importance of taking into account neuroendocrine tumors in our differential diagnostic considerations. At the same time, we want to highlight that, according to ESMO recommendations, we should preferentially use 68Ga-DOTATOC PET/CT for the diagnosis instead of scintigraphic examination (111In-Octreoscan).

• MeSH
• Abdominal Pain etiology   MeSH
• Chromogranin A analysis   MeSH
• Gastrinoma * surgery   diagnostic imaging   pathology   MeSH
• Gastrins analysis   MeSH
• Proton Pump Inhibitors therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Duodenal Neoplasms * surgery   diagnostic imaging   pathology   MeSH
• Neuroendocrine Tumors surgery   diagnostic imaging   classification   pathology   MeSH
• Positron Emission Tomography Computed Tomography methods   MeSH
• Zollinger-Ellison Syndrome diagnosis   etiology   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Chromogranin A analysis   blood   MeSH
• Carcinoid Tumor * diagnostic imaging   surgery   pathology   MeSH
• Humans MeSH
• Metastasectomy MeSH
• Bronchial Neoplasms diagnostic imaging   surgery   pathology   MeSH
• Neuroendocrine Tumors diagnosis   surgery   pathology   MeSH
• Retroperitoneal Space surgery   pathology   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Chromogranin A blood   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Hypercalcemia diagnosis   etiology   MeSH
• Hyperparathyroidism diagnostic imaging   genetics   MeSH
• Humans MeSH
• Multiple Endocrine Neoplasia Type 1 diagnostic imaging   genetics   therapy   MeSH
• Pituitary Neoplasms diagnostic imaging   pathology   MeSH
• Parathyroid Neoplasms genetics   pathology   therapy   MeSH
• Pancreatic Neoplasms diagnostic imaging   pathology   diagnostic imaging   pathology   MeSH
• Treatment Refusal MeSH
• Parathyroid Glands pathology   MeSH
• Parathyroidectomy MeSH
• Hyperparathyroidism, Primary diagnostic imaging   etiology   genetics   MeSH
• Prognosis MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Chemotherapy, Adjuvant methods   MeSH
• Radiotherapy Dosage MeSH
• Chromogranin A analysis   blood   MeSH
• Gastrins blood   MeSH
• Gastritis, Atrophic pathology   MeSH
• Gastroscopy methods   standards   MeSH
• Anemia, Hypochromic diagnostic imaging   etiology   MeSH
• Middle Aged MeSH
• Neoplasm Metastasis diagnostic imaging   drug therapy   radiotherapy   MeSH
• Biomarkers, Tumor blood   MeSH
• Stomach Neoplasms diagnostic imaging   drug therapy   physiopathology   pathology   MeSH
• Neuroendocrine Tumors classification   pathology   MeSH
• Anemia, Pernicious diagnosis   drug therapy   MeSH
• Prognosis MeSH
• Radiotherapy MeSH
• Somatostatin analogs & derivatives   administration & dosage   pharmacology   MeSH
• Neoplasm Grading MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Male MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Radiotherapy Dosage MeSH
• Chromogranin A blood   MeSH
• Gastrinoma * diagnostic imaging   drug therapy   radiotherapy   MeSH
• Gastrins blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor blood   MeSH
• Duodenal Neoplasms MeSH
• Neuroendocrine Tumors MeSH
• Octreotide administration & dosage   MeSH
• Antineoplastic Combined Chemotherapy Protocols adverse effects   therapeutic use   MeSH
• Radiotherapy methods   MeSH
• Intestinal Neoplasms diagnostic imaging   pathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Feochromocytóm (FEO) a paraganglióm (PGL) sú zriedkavé katecholamíny produkujúce neuroendokrinné tumory vychádzajúce z drene nadobličky alebo z extraadrenálnych sympatikových a parasympatikových ganglií. Vo väčšine prípadov FEO/PGL ide o benígne tumory, avšak metastatické ochorenie nie je výnimkou, predovšetkým u pacientov so špecifickým genetickým pozadím. Aj keď FEO/PGL boli popísané už pred viac ako storočím, diagnostika a liečba metastatického ochorenia sú stále problematické. Pokrok v porozumení molekulárnym a metabolickým zmenám asociovaným s tumorigenézou nás vedie bližšie k identifikácii podstaty týchto tumorov. Nové poznatky umožnili vyvinúť presnejšie diagnostické metódy a identifikovať molekulárne terapeutické ciele, ktoré by mali prispieť k zlepšeniu starostlivosti o pacientov s metastatickým FEO/PGL.

Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare catecholamine-producing neuroendocrine tumors arising from adrenal medulla or extra-adrenal sympathetic and parasympathetic ganglia. Most of the PHEOs/PGLs are benign tumors, but metastatic disease is common, especially in patients with particular genetic background. Although PHEOs/PGLs were described more than a century ago, diagnosis and therapy of metastatic disease are still challenging. Advances in understanding molecular and metabolic changes associated with tumorigenesis lead us to identification of the background of these tumors. Novel information allowed for development of more precise diagnostic methods and molecular therapeutic targets identification, which will improve care of patients with metastatic PHEO/PGL.

• MeSH
• Chromogranin A analysis   physiology   MeSH
• Molecular Targeted Therapy MeSH
• Diagnosis, Differential MeSH
• Dopamine analysis   MeSH
• Pheochromocytoma * diagnosis   therapy   MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Mutation genetics   MeSH
• Neuroendocrine Tumors MeSH
• Paraganglioma * diagnosis   therapy   MeSH
• Radiotherapy MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

This work discusses the clinical performance of chromogranin A, free metanephrine and normetanephrine determination in plasma using a radioimmunoanalytical methods for the diagnosis of pheochromocytoma and paraganglioma. Blood samples were collected from 55 patients (46 pheochromocytomas, 9 paragangliomas). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The comparative group without a diagnosis of pheochromocytoma/paraganglioma consisted of 36 pheochromocytoma/paraganglioma patients more than 4 months after adrenal gland surgery, and of 87 patients, 16 of them with multiple endocrine neoplasia, 9 with medullary and 5 with parafolicullar carcinoma of the thyroid gland. The rest were patients with various adrenal gland disorders. Chromogranin A, metanephrine and normetanephrine were determined in the EDTA-plasma using a radioimmunoassay kits Cisbio Bioassays, France and IBL International GmbH, Germany. Clinical sensitivity was 96 % for the combination of metanephrine and normetanephrine, and 93 % for chromogranin A. Clinical specificity was 100 % for the combination metanephrine and normetanephrine, and 96 % for chromogranin A. Falsely elevated levels of chromogranin A were observed in 1 patient with chronic renal insufficiency and 9 analyses were influenced by the administration of proton pump inhibitors. These results were excluded of CGA specificity. Both the combination of plasma free metanephrine, normetanephrine and chromogranin A as determined by radioimmunoassays, which are simple without the necessity of special laboratory material, are effective markers of pheochromocytoma or paraganglioma. Chromogranin A exerts association to malignity and all markers are associated with tumor mass.

• MeSH
• Chromogranin A blood   MeSH
• Adult MeSH
• Pheochromocytoma blood   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Metanephrine blood   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Biomarkers, Tumor blood   MeSH
• Adrenal Gland Neoplasms blood   diagnosis   MeSH
• Normetanephrine blood   MeSH
• Radioimmunoassay methods   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH