Refine
Has Fulltext
- yes (69)
Is part of the Bibliography
- yes (69)
Year of publication
Document Type
- Journal article (68)
- Conference Proceeding (1)
Language
- English (69) (remove)
Keywords
- adrenocortical carcinoma (10)
- obesity (5)
- metabolomics (4)
- 18F-FDG (3)
- CXCR4 (3)
- Cushing’s syndrome (3)
- FGFR (3)
- PET (3)
- adrenocortical cancer (3)
- biomarker (3)
- cortisol (3)
- hypercortisolism (3)
- liraglutide (3)
- paraganglioma (3)
- pheochromocytoma (3)
- positron emission tomography (3)
- prognosis (3)
- therapy (3)
- vandetanib (3)
- ACTH (2)
- C-X-C motif chemokine receptor 4 (2)
- CYP2W1 (2)
- Cushing’s disease (2)
- FGF-pathway (2)
- PPGL (2)
- Positronen-Emissions-Tomografie (2)
- TKI (2)
- [68Ga]PentixaFor (2)
- adenomas (2)
- adrenal cancer (2)
- adrenal tumours (2)
- adrenocortical tumors (2)
- cancer (2)
- carcinomas (2)
- cardiovascular events (2)
- chemokine receptor (2)
- endoradiotherapy (2)
- gastric bypass (2)
- immune response (2)
- immunohistochemistry (2)
- immunotherapy (2)
- machine learning (2)
- medullary thyroid carcinoma (2)
- mitotane (2)
- mortality (2)
- pediatric adrenocortical cancer (2)
- pediatric adrenocortical tumor (2)
- peptide tyrosine tyrosine (PYY) (2)
- recurrence (2)
- theranostics (2)
- treatment (2)
- tyrosine kinase inhibitor (2)
- 2- deoxy-2-(18F)fluoro-D-glucose (1)
- 2-deoxy-2-(18F)fluoro-D-glucose (1)
- ALT (1)
- ATRX (1)
- Adrenocortial carcinomas (1)
- Adrenocortical Carcinoma (1)
- Antigen 4 (1)
- Autoimmune-Diseases (1)
- BIRC7 (1)
- BRAF(V600E) mutation (1)
- Biochemical-Diagnosis (1)
- C-terminal HSP90 inhibitors (1)
- CCR7 (1)
- CRH stimulation test (1)
- CTNNB1 (1)
- CXCR7 (1)
- CYP11B enzymes (1)
- CYP2B6 (1)
- Cell lung canger (1)
- Contrast-enhanced CT (1)
- Copeptin (1)
- Cushing (1)
- Cushing's disease (1)
- Cushings syndrome (1)
- Dendritic Cells (1)
- Diagnosis (1)
- Disease prevalence (1)
- EMT (1)
- F-18-FDG PET/CT (1)
- FGF21 (1)
- FGFR-inhibitors (1)
- Fibroblast Growth Factor-21 (1)
- FoxP3 Expression (1)
- GLP-1 (1)
- Immune-System (1)
- Immunological Self-Tolerance (1)
- Klotho-related molecules (1)
- LND (1)
- LNE (1)
- MASS (1)
- MR (1)
- MTL30 (1)
- Medicine (1)
- Medizin (1)
- Medullärer Schilddrüsenkrebs (1)
- Men (1)
- Metanephrine (1)
- Methodological quality (1)
- Multiple-Sclerosis (1)
- N-terminal HSP90 inhibitors (1)
- NAFLD (1)
- NASH (1)
- NMR (1)
- NOP10 (1)
- NR3C1 (1)
- Normetanephrine (1)
- PD-L1 (1)
- PF-05231023 (1)
- PYY3-36 (1)
- Paraganglioma (1)
- Plasma (1)
- Positron-emission-tomography (1)
- RNA Expression (1)
- RNAScope (1)
- RYGB (1)
- Resistance (1)
- Roux-en-Y Gastric Bypass (1)
- Roux-en-Y gastric bypass (1)
- Roux-en-Y gastric bypass surgery (1)
- SNP (1)
- SOAT1 (1)
- Sex-Hormones (1)
- Society (1)
- Spin echo (1)
- Suppressive Function (1)
- Systemic-Lupus-Erythematosus (1)
- TERT (1)
- Test accuracy (1)
- USP8 (1)
- Utility (1)
- [11C]-Choline PET/CT (1)
- [11C]-Methionine (1)
- [177Lu]/[90Y]PentixaTher (1)
- [177Lu]PentixaTher (1)
- [18F]FDG-PET-CT (1)
- [90Y]PentixaTher (1)
- [99mTc]-Sestamibi scan (1)
- abdominal lymph node metastases (1)
- adjuvant platinum-based chemotherapy (1)
- adjuvant treatment (1)
- adrenal (1)
- adrenal cortex hormones (1)
- adrenal cortex neoplasms (1)
- adrenal gland (1)
- adrenal glands (1)
- adrenal imaging (1)
- adrenal incidentaloma (1)
- adrenal surgery (1)
- adrenal tumor (1)
- adrenal tumors (1)
- adrenalectomia (1)
- adrenocortical (1)
- adrenocortical adenocarcinoma (1)
- adrenocortical carcinoma (ACC) (1)
- adrenocortical development (1)
- adrenocortical tissues (1)
- aldosterone (1)
- association (1)
- autoantibodies (1)
- autonomous cortisol secretion (1)
- balance (1)
- bioinformatic clustering (1)
- biomarker prediction (1)
- biomarkers (1)
- blood pressure (1)
- branched-chain amino acids (1)
- cancer detection (1)
- cancer diagnosis (1)
- cancer treatment (1)
- cancer-testis antigens (1)
- carcinogenesis (1)
- carcinoma (1)
- carcinoma metastases to pancreas (1)
- cardiovascular risk factors (1)
- caspase-3 (1)
- catecholamines (1)
- catenin (1)
- cells (1)
- cholesterol metabolism (1)
- chromosomes (1)
- circulating microRNA (1)
- combination (1)
- comparability (1)
- comparative genomic hybridization (1)
- complication (1)
- confounders (1)
- copeptin (1)
- cortisol-producing adenoma (1)
- cytoplasmic staining (1)
- deubiquitinases (1)
- dexamethasone suppression test (1)
- diabetes insipidus (1)
- diagnosis (1)
- disease score (1)
- disease severity (1)
- dissection (1)
- distant metastases (1)
- dogs (1)
- drug therapy (1)
- early prognosis (1)
- ectopic (1)
- efficacy (1)
- endogenous hypercortisolism (1)
- epithelial markers (1)
- expression (1)
- feature selection (1)
- focused surgical approach (1)
- follow-up (1)
- genetic loci (1)
- glucocorticoid excess (1)
- guidelines (1)
- high dose dexamethasone suppression test (1)
- high-resolution analysis (1)
- hormones (1)
- hypothalamic gene expression (1)
- imaging (1)
- immune check inhibitor (1)
- immune checkpoint inhibitor (ICI) (1)
- immunity (1)
- immunohistochemistry techniques (1)
- in silico analysis (1)
- insulin resistance (1)
- intragastric balloon (1)
- isturisa (1)
- kidney disease (1)
- kinase (1)
- kinases (1)
- liquid chromatography–tandem mass spectrometry (LC–MS/MS) (1)
- liver resection (1)
- livin (1)
- lymph node dissection (1)
- lymphadenectomy (1)
- lymphocytes (1)
- malignant tumors (1)
- management (1)
- mass spectrometry (1)
- mass spectronomy (1)
- medical therapy (1)
- mesenchymal markers (1)
- meta-analysis (1)
- metyrapone (1)
- miR-182-5p (1)
- miR-183 cluster (1)
- miR-483-5p (1)
- miRNA (1)
- molecular diagnostics (1)
- morbidity (1)
- multicenter (1)
- multiple myeloma (1)
- mutation (1)
- mutation triggers (1)
- neuroblastoma – diagnosis (1)
- neutral loss (1)
- normal adrenal glands (1)
- normal values (1)
- notch signaling (1)
- nuclear staining (1)
- operation (1)
- osilodrostat (1)
- osmotic stimulation (1)
- outcome (1)
- paired (1)
- papillary (1)
- papillary thyroid carcinoma (PTC) (1)
- parathyroid adenoma (1)
- parathyroid carcinoma (1)
- pathogenesis (1)
- patient survival (1)
- pediatric (1)
- pediatric adrenocortical adenoma (1)
- pediatric adrenocortical carcinoma (1)
- pembrolizumab (1)
- peptide tyrosine tyrosine 3-36 (PYY3-36) (1)
- peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) (1)
- personalized medicine (1)
- phosphatidylcholines (1)
- phosphorylation (1)
- pituitary adenomas (1)
- pituitary gland (1)
- plasma (1)
- plasma NMR (1)
- polarization (1)
- preanalytical conditions (1)
- precision medicine (1)
- predictive marker (1)
- primary hyperparathyroidism (1)
- primary polydipsia (1)
- prognostic biomarker (1)
- prognostic factors (1)
- prognostic marker (1)
- prospective (1)
- prostate cancer (1)
- protein expression (1)
- radical resection (1)
- radioiodine (1)
- radioiodine therapy (1)
- radiotherapy (1)
- radiotherapy (RT) (1)
- recurrence free survival (1)
- recurrence-free survival (1)
- reference data (1)
- repeated surgery (1)
- retrospective study (1)
- review (1)
- rodent model (1)
- rygb (1)
- selpercatinib (1)
- serum (1)
- signs and symptoms (1)
- sleeve gastrectomy (1)
- somatic mutations (1)
- sphingolipids (1)
- steroid measurement (1)
- sudden cardiac death (1)
- super-obesity (1)
- surgery (1)
- surgical oncology (1)
- surgical treatment (1)
- survival analysis (1)
- t-lymphocytes (1)
- targeted metabolomics (1)
- targeted treatment (1)
- telomeres (1)
- thyroid carcinoma (TC) (1)
- timing (1)
- transgenic rats (1)
- tumor microenvironment (1)
- tumor-infiltrating (1)
- tumors (1)
- tyrosine kinase inhibitor (TKI) (1)
- unsupervised clustering (1)
- urine (1)
- volume (1)
Institute
- Medizinische Klinik und Poliklinik I (67)
- Comprehensive Cancer Center Mainfranken (16)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (14)
- Pathologisches Institut (14)
- Klinik und Poliklinik für Nuklearmedizin (13)
- Kinderklinik und Poliklinik (5)
- Medizinische Klinik und Poliklinik II (5)
- Theodor-Boveri-Institut für Biowissenschaften (5)
- Urologische Klinik und Poliklinik (4)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (3)
Sonstige beteiligte Institutionen
Background
Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising.
Materials and Methods
Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable.
Results
PD-L1 TPS≥50% was observed in 42% of ATC and 26% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30%) than in PDTC (5%; p<0.01) and NT (0%, p<0.001). 53% of PDTC samples had PD-L1 expression ≤5%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS.
Conclusion
High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation.
Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R.
The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression.
Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform β more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability.
In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.
Mitotane is the only approved drug for advanced adrenocortical carcinoma (ACC) and no biomarkers are available to predict attainment of therapeutic plasma concentrations and clinical response. Aim of the study was to evaluate the suitability of cytochrome P450(CYP)2W1 and CYP2B6 single nucleotide polymorphisms (SNPs) as biomarkers. A multicenter cohort study including 182 ACC patients (F/M = 121/61) treated with mitotane monotherapy after radical resection (group A, n = 103) or in not completely resectable, recurrent or advanced disease (group B, n = 79) was performed. CYP2W1*2, CYP2W1*6, CYP2B6*6 and CYP2B6 rs4803419 were genotyped in germline DNA. Mitotane blood levels were measured regularly. Response to therapy was evaluated as time to progression (TTP) and disease control rate (DCR). Among investigated SNPs, CYP2W1*6 and CYP2B6*6 correlated with mitotane treatment only in group B. Patients with CYP2W1*6 (n = 21) achieved less frequently therapeutic mitotane levels (>14 mg/L) than those with wild type (WT) allele (76.2% vs 51.7%, p = 0.051) and experienced shorter TTP (HR = 2.10, p = 0.019) and lower DCR (chi-square = 6.948, p = 0.008). By contrast, 55% of patients with CYP2B6*6 vs. 28.2% WT (p = 0.016) achieved therapeutic range. Combined, a higher rate of patients with CYP2W1*6WT+CYP2B6*6 (60.6%) achieved mitotane therapeutic range (p = 0.034). In not completely resectable, recurrent or advanced ACC, CYP2W1*6 SNP was associated with a reduced probability to reach mitotane therapeutic range and lower response rates, whereas CYP2B6*6 correlated with higher mitotane levels. The association of these SNPs may predict individual response to mitotane.
International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers
(2021)
Approximately 20% of patients diagnosed with a phaeochromocytoma or paraganglioma carry a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. When a pathogenic SDHx mutation is identified in an affected patient, genetic counselling is proposed for first-degree relatives. Optimal initial evaluation and follow-up of people who are asymptomatic but might carry SDHx mutations have not yet been agreed. Thus, we established an international consensus algorithm of clinical, biochemical and imaging screening at diagnosis and during surveillance for both adults and children. An international panel of 29 experts from 12 countries was assembled, and the Delphi method was used to reach a consensus on 41 statements. This Consensus Statement covers a range of topics, including age of first genetic testing, appropriate biochemical and imaging tests for initial tumour screening and follow-up, screening for rare SDHx-related tumours and management of elderly people who have an SDHx mutation. This Consensus Statement focuses on the management of asymptomatic SDHx mutation carriers and provides clinicians with much-needed guidance. The standardization of practice will enable prospective studies in the near future.
Context:
Adrenal tumors have a prevalence of around 2% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2–11% of incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents a diagnostic challenge in patients with adrenal incidentalomas, with tumor size, imaging, and even histology all providing unsatisfactory predictive values.
Objective:
Here we developed a novel steroid metabolomic approach, mass spectrometry-based steroid profiling followed by machine learning analysis, and examined its diagnostic value for the detection of adrenal malignancy.
Design:
Quantification of 32 distinct adrenal derived steroids was carried out by gas chromatography/mass spectrometry in 24-h urine samples from 102 ACA patients (age range 19–84 yr) and 45 ACC patients (20–80 yr). Underlying diagnosis was ascertained by histology and metastasis in ACC and by clinical follow-up [median duration 52 (range 26–201) months] without evidence of metastasis in ACA. Steroid excretion data were subjected to generalized matrix learning vector quantization (GMLVQ) to identify the most discriminative steroids.
Results:
Steroid profiling revealed a pattern of predominantly immature, early-stage steroidogenesis in ACC. GMLVQ analysis identified a subset of nine steroids that performed best in differentiating ACA from ACC. Receiver-operating characteristics analysis of GMLVQ results demonstrated sensitivity = specificity = 90% (area under the curve = 0.97) employing all 32 steroids and sensitivity = specificity = 88% (area under the curve = 0.96) when using only the nine most differentiating markers.
Conclusions:
Urine steroid metabolomics is a novel, highly sensitive, and specific biomarker tool for discriminating benign from malignant adrenal tumors, with obvious promise for the diagnostic work-up of patients with adrenal incidentalomas.
Although bariatric surgery is known to change the metabolome, it is unclear if this is specific for the intervention or a consequence of the induced bodyweight loss. As the weight loss after Roux-en-Y Gastric Bypass (RYGB) can hardly be mimicked with an evenly effective diet in humans, translational research efforts might be helpful. A group of 188 plasma metabolites of 46 patients from the randomized controlled Würzburg Adipositas Study (WAS) and from RYGB-treated rats (n = 6) as well as body-weight-matched controls (n = 7) were measured using liquid chromatography tandem mass spectrometry. WAS participants were randomized into intensive lifestyle modification (LS, n = 24) or RYGB (OP, n = 22). In patients in the WAS cohort, only bariatric surgery achieved a sustained weight loss (BMI −34.3% (OP) vs. −1.2% (LS), p ≤ 0.01). An explicit shift in the metabolomic profile was found in 57 metabolites in the human cohort and in 62 metabolites in the rodent model. Significantly higher levels of sphingolipids and lecithins were detected in both surgical groups but not in the conservatively treated human and animal groups. RYGB leads to a characteristic metabolomic profile, which differs distinctly from that following non-surgical intervention. Analysis of the human and rat data revealed that RYGB induces specific changes in the metabolome independent of weight loss.
A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence.
Background:
Metastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC.
Methods:
A retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included.
Results:
Seventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival.
Conclusions:
Liver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome.
Background
Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin.
Case presentation
Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred.
Conclusion
Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.
Purpose
Pheochromocytomas and Paragangliomas (PPGL) result in chronic catecholamine excess and serious health complications. A recent study obtained a metabolic signature in plasma from PPGL patients; however, its targeted nature may have generated an incomplete picture and a broader approach could provide additional insights. We aimed to characterize the plasma metabolome of PPGL patients before and after surgery, using an untargeted approach, and to broaden the scope of the investigated metabolic impact of these tumors.
Design
A cohort of 36 PPGL patients was investigated. Blood plasma samples were collected before and after surgical tumor removal, in association with clinical and tumor characteristics.
Methods
Plasma samples were analyzed using untargeted nuclear magnetic resonance (NMR) spectroscopy metabolomics. The data were evaluated using a combination of uni- and multi-variate statistical methods.
Results
Before surgery, patients with a nonadrenergic tumor could be distinguished from those with an adrenergic tumor based on their metabolic profiles. Tyrosine levels were significantly higher in patients with high compared to those with low BMI. Comparing subgroups of pre-operative samples with their post-operative counterparts, we found a metabolic signature that included ketone bodies, glucose, organic acids, methanol, dimethyl sulfone and amino acids. Three signals with unclear identities were found to be affected.
Conclusions
Our study suggests that the pathways of glucose and ketone body homeostasis are affected in PPGL patients. BMI-related metabolite levels were also found to be altered, potentially linking muscle atrophy to PPGL. At baseline, patient metabolomes could be discriminated based on their catecholamine phenotype.