BACKGROUND: Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype. METHODS: We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines. RESULTS: According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; P=0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; P=0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis. CONCLUSIONS: We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.
- MeSH
- adrenergní látky MeSH
- ateroskleróza * komplikace MeSH
- fenotyp MeSH
- feochromocytom * diagnóza MeSH
- infarkt myokardu * MeSH
- kardiomyopatie * MeSH
- katecholaminy MeSH
- lidé MeSH
- metanefrin MeSH
- nádory nadledvin * patologie MeSH
- paragangliom * komplikace MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.
- MeSH
- dítě MeSH
- dospělí MeSH
- feochromocytom * genetika terapie diagnóza MeSH
- lidé MeSH
- nádory nadledvin * genetika terapie diagnóza MeSH
- paragangliom * genetika terapie MeSH
- sukcinátdehydrogenasa genetika MeSH
- zárodečné mutace genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanom * epidemiologie etiologie diagnóza MeSH
- nádory kůže * etiologie komplikace MeSH
- nedostatek vitaminu D * komplikace epidemiologie MeSH
- retrospektivní studie MeSH
- sekundární malignity * epidemiologie etiologie MeSH
- vitamin D škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Breast cancer is the most frequently diagnosed cancer in women worldwide. Although dramatically increased survival rates of early diagnosed cases have been observed, late diagnosed patients and metastatic cancer may still be considered fatal. The present study's main focus was on cancer‐associated fibroblasts (CAFs) which is an active component of the tumor microenvironment (TME) regulating the breast cancer ecosystem. Transcriptomic profiling and analysis of CAFs isolated from breast cancer skin metastasis, cutaneous basal cell carcinoma, and squamous cell carcinoma unravelled major gene candidates such as IL6, VEGFA and MFGE8 that induced co‐expression of keratins‐8/‐14 in the EM‐G3 cell line derived from infiltrating ductal breast carcinoma. Western blot analysis of selected keratins (keratin‐8, ‐14, ‐18, ‐19) and epithelial‐mesenchymal transition‐associated markers (SLUG, SNAIL, ZEB1, E‐/N‐cadherin, vimentin) revealed specific responses pointing to certain heterogeneity of the studied CAF populations. Experimental in vitro treatment using neutralizing antibodies against IL-6, VEGF‐A and MFGE8 attenuated the modulatory effect of CAFs on EM‐G3 cells. The present study provided novel data in characterizing and understanding the interactions between CAFs and EM‐G3 cells in vitro. CAFs of different origins support the pro‐inflammatory microenvironment and influence the biology of breast cancer cells. This observation potentially holds significant interest for the development of novel, clinically relevant approaches targeting the TME in breast cancer. Furthermore, its implications extend beyond breast cancer and have the potential to impact a wide range of other cancer types.
- MeSH
- antigeny povrchové MeSH
- fibroblasty asociované s nádorem * metabolismus MeSH
- fibroblasty metabolismus MeSH
- keratiny genetika metabolismus MeSH
- lidé MeSH
- maligní melanom kůže MeSH
- MFC-7 buňky MeSH
- mléčné bílkoviny genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí genetika MeSH
- nádory prsu * farmakoterapie genetika metabolismus MeSH
- prognóza MeSH
- transkriptom MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
We report a very unusual case of melanocytic neoplasm appearing clinically as a 0.5-cm dome-shaped pigmented papule on the chest of a 63-year-old man. Microscopically, it was an asymmetric, entirely dermally based neoplasm characterized by a multinodular, vaguely plexiform architecture composed of moderately pleomorphic spindled melanocytes with ample, dusty pigmented cytoplasm and scattered multinucleated cells. The tumor cells were strongly positive for Melan-A, HMB45, S100, and PRAME, whereas p16 showed diffuse nuclear loss. β-catenin presented a strong and diffuse cytoplasmic staining, while nuclei were negative. Despite an increased cellularity, mitotic count was low (1/mm 2 ). Fluorescence in situ hybridization revealed no copy number alteration in melanoma-related genes ( CDKN2A, MYB, MYC, CCND1 and RREB1 ). DNA and RNA sequencing identified KIT c.2458G>T and APC c.6709C>T mutations. No further genetic alteration was detected including TERT-promoter (TERT-p ) hot-spot mutation. A re-excision was performed. A sentinel lymph node biopsy was negative. Clinical investigations revealed no extracutaneous involvement. The patient is disease-free after a follow-up period of 8 months. Given the peculiar morphologic and molecular findings, we hypothesize the lesion may represent a novel subtype of an intermediate grade melanocytic tumor (melanocytoma).
- MeSH
- antigeny nádorové MeSH
- biopsie sentinelové lymfatické uzliny MeSH
- hybridizace in situ fluorescenční MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanocyty patologie MeSH
- melanom * patologie MeSH
- mutace MeSH
- nádory kůže * patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanom * epidemiologie etiologie diagnóza MeSH
- nádory kůže * etiologie komplikace MeSH
- nedostatek vitaminu D * komplikace epidemiologie MeSH
- retrospektivní studie MeSH
- sekundární malignity * epidemiologie etiologie MeSH
- vitamin D škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND AND OBJECTIVES: Intratumoral hemorrhage (ITH) in vestibular schwannoma (VS) after stereotactic radiosurgery (SRS) is exceedingly rare. The aim of this study was to define its incidence and describe its management and outcomes in this subset of patients. METHODS: A retrospective multi-institutional study was conducted, screening 9565 patients with VS managed with SRS at 10 centers affiliated with the International Radiosurgery Research Foundation. RESULTS: A total of 25 patients developed ITH (cumulative incidence of 0.26%) after SRS management, with a median ITH size of 1.2 cm 3 . Most of the patients had Koos grade II-IV VS, and the median age was 62 years. After ITH development, 21 patients were observed, 2 had urgent surgical intervention, and 2 were initially observed and had late resection because of delayed hemorrhagic expansion and/or clinical deterioration. The histopathology of the resected tumors showed typical, benign VS histology without sclerosis, along with chronic inflammatory cells and multiple fragments of hemorrhage. At the last follow-up, 17 patients improved and 8 remained clinically stable. CONCLUSION: ITH after SRS for VS is extremely rare but has various clinical manifestations and severity. The management paradigm should be individualized based on patient-specific factors, rapidity of clinical and/or radiographic progression, ITH expansion, and overall patient condition.
- MeSH
- krvácení chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrochirurgie MeSH
- následné studie MeSH
- radiochirurgie * škodlivé účinky MeSH
- retrospektivní studie MeSH
- vestibulární schwannom * chirurgie patologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.
- MeSH
- dítě MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory kraniálních nervů * chirurgie MeSH
- následné studie MeSH
- neurilemom * diagnostické zobrazování radioterapie chirurgie MeSH
- radiochirurgie * metody MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- MeSH
- lidé MeSH
- nervus radialis * diagnostické zobrazování MeSH
- neurilemom * diagnostické zobrazování chirurgie MeSH
- reflex fyziologie MeSH
- ultrasonografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Immunotherapy and targeted therapy are currently two alternative backbones in the therapy of BRAF-mutated malignant melanoma. However, predictive biomarkers that would help with treatment selection are lacking. METHODS: This retrospective study investigated outcomes of anti-programmed death receptor-1 monotherapy and targeted therapy in the first-line setting in patients with metastatic BRAF-mutated melanoma, focusing on clinical and laboratory parameters associated with treatment outcome. RESULTS: Data from 174 patients were analysed. The median progression-free survival (PFS) was 17.0 months (95% CI; 8-39) and 12.5 months (95% CI; 9-14.2) for immunotherapy and targeted therapy, respectively. The 3-year PFS rate was 39% for immunotherapy and 25% for targeted therapy. The objective response rate was 72% and 51% for targeted therapy and immunotherapy. The median overall (OS) survival for immunotherapy has not been reached and was 23.6 months (95% CI; 16.1-38.2) for targeted therapy, with a 3-year survival rate of 63% and 40%, respectively. In a univariate analysis, age < 70 years, a higher number of metastatic sites, elevated serum LDH and a neutrophil-lymphocyte ratio above the cut-off value were associated with inferior PFS regardless of the therapy received, but only serum LDH level and the presence of lung metastases remained significant predictors of PFS in a multivariate analysis. CONCLUSIONS: Present real-world data document the high effectiveness of immunotherapy and targeted therapy. Although targeted therapy had higher response rates, immunotherapy improved PFS and OS. While the prognostic value of LDH was confirmed, the potential use of blood cell count-derived parameters to predict outcomes needs further investigation.
