scholarly journals Succinate Dehydrogenase B Gene Mutations Predict Survival in Patients with Malignant Pheochromocytomas or Paragangliomas

2007 ◽  
Vol 92 (10) ◽  
pp. 3822-3828 ◽  
Author(s):  
Laurence Amar ◽  
Eric Baudin ◽  
Nelly Burnichon ◽  
Séverine Peyrard ◽  
Stéphane Silvera ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Retrospective Cohort ◽  
Prognostic Value ◽  
Clinical Course ◽  
Malignant Tumors ◽  
Gene Mutations ◽  
Germline Mutations ◽  
Adrenal Tumors ◽  
Probability Of Survival ◽  
Sporadic Tumors

Abstract Context: Pheochromocytomas and paragangliomas may be malignant either at presentation or during recurrence, but the clinical course of malignant tumors is unpredictable. Objective: The objective was to analyze survival according to clinical characteristics at diagnosis of malignancy and the presence or absence of SDHB mutations. Design: This was a retrospective cohort study. Setting and Participants: A total of 54 patients with malignant tumors were included. Malignancy was scored according to the presence of metastases or histologically documented lymph node invasion. Main Outcome Measures: The main outcome was the specific survival after the diagnosis of the first metastasis. Results: Germline mutations were identified in SDHB (n = 23, including 21 patients with apparent sporadic tumors) and VHL (n = 1) genes, and two patients had neurofibromatosis 1. Patients were followed up from the diagnosis of primary tumor and from the diagnosis of the first metastasis to the present or to death with medians of 79 [interquartile range (IQR) 24; 190] and 39 [IQR 14; 94] months, respectively. The 5-yr probability of survival after the diagnosis of the first metastasis was 0.55 (95% confidence interval 0.39–0.69). Patients with SDHB mutations were younger, more frequently had extra-adrenal tumors, and had a shorter metanephrine excretion doubling time. The presence of SDHB mutations was significantly and independently associated with mortality (relative risk 2.7; 95% confidence interval 1.2, 6.4; P = 0.021). Conclusion: SDHB mutations, frequent in patients with malignant pheochromocytomas or paragangliomas, are associated with shorter survival. Therefore, SDHB genetic testing may be of prognostic value for such patients, even those with an apparent sporadic and/or benign presentation at diagnosis.

scholarly journals Molecular-genetic and phenotypic characteristics of desmoid-type fibromatosis

2019 ◽  
pp. 9-15
Author(s):  
T.A. Muzaffarova ◽  
O.V. Novikova ◽  
I.Yu. Sachkov ◽  
F.M. Kipkeeva ◽  
E.K. Ginter ◽  
...  
Keyword(s):  
Clinical Course ◽  
Age Of Onset ◽  
Molecular Genetic ◽  
Germline Mutations ◽  
Apc Gene ◽  
Phenotypic Characteristics ◽  
Potential Significance ◽  
Desmoid Fibromatosis ◽  
Apc Mutations ◽  
Sporadic Tumors

Desmoid-type fibromatosis (DF) is a rare mesenchymal tumor occurring in only 2 to 4 people per 1,000,000 population a year. Desmoid tumors are either seen sporadically or in individuals with familial adenomatous polyposis (FAP). The etiology of sporadic DF is uncertain. The aim of this study was to estimate the potential significance of germline mutations in the APC gene in patients with sporadic DF. APC exons were amplified, studied using conformation sensitive gel electrophoresis and then Sanger-sequenced. The obtained data were processed in Statistica 10. Mutations were detected in 6 (12%) of 51 participants with sporadic DF. Those 6 patients shared a typical DF phenotype characterized by early age of onset (5.8 years on average, in contrast to the patients without APC mutations, who developed DF at 19 years of age; p = 0.02), severe clinical course, multifocal localization on the trunk, and poor prognosis. All of the detected APC mutations were localized to the 3'-end of the gene. For the purpose of comparison, we analyzed a sample of 12 patients with FAP-associated DF. Of those patients, 6 carried mutations in the APC gene. In the analyzed sample, the patients with FAP and the mutant APC gene developed DF at older age (35 years) than the patients with sporadic DF (p = 0.004) and their tumors were not multifocal. This means that sporadic and FAP-associated desmoids have different phenotypes in patients with APC mutations. Patients with sporadic tumors have mutations at the 3'-end of the APC gene more often than individuals with FAP-associated DF. To our knowledge, this is the first study to characterize the subtype of sporadic desmoid fibromatosis phenotypically determined by germline mutations in the APC gene.

scholarly journals AB0666 PROGNOSTIC VALUE OF SERUM KREBS VON DEN LUNGEN-6 GLYCOPROTEIN CIRCULATING LEVELS IN COVID-19 PNEUMONIA: A PROSPECTIVE COHORT STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1365.1-1365
Author(s):  
D. Lobo Prat ◽  
I. Castellví ◽  
D. Castillo ◽  
S. Orozco ◽  
A. Mariscal ◽  
...  
Keyword(s):  
Cohort Study ◽  
Retrospective Cohort ◽  
Prognostic Value ◽  
Screening Tool ◽  
Clinical Course ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Descriptive Study ◽  
Circulating Levels

Background:Currently, there are no biomarkers to predict respiratory worsening in patients with Coronavirus infectious disease, 2019 (COVID- 19) pneumonia.Objectives:We aimed to determine the prognostic value of Krebs von de Lungen-6 circulating serum levels (sKL-6) predicting COVID- 19 evolving trends.Methods:We prospectively analyzed the clinical and laboratory characteristics of 375 COVID- 19 patients with mild lung disease on admission. sKL-6 was obtained in all patients at baseline and compared among patients with respiratory worsening.Results:45.1% of patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were higher in patients who had respiratory worsening (median [IQR] 303 [209-449] vs. 285.5 [15.8-5724], P=0.068). The best sKL-6 cut-off point was 408 U/mL (area under the curve 0.55; 33% sensitivity, 79% specificity). Independent predictors of respiratory worsening were sKL-6 serum levels, age >51 years, time hospitalized, and dyspnea on admission. Patients with baseline sKL-6 ≥ 408 U/mL had a 39% higher risk of developing respiratory aggravation seven days after admission. In patients with serial determinations, sKL-6 was also higher in those who subsequently worsened (median [IQR] 330 [219-460] vs 290.5 [193-396]; p<0.02).Conclusion:sKL-6 has a low sensibility to predict respiratory worsening in patients with mild COVID-19 pneumonia. Baseline sKL-6 ≥ 408 U/mL is associated to a higher risk of respiratory worsening. sKL-6 levels are not useful as a screening tool to stratify patients on admission but further research is needed to investigate if serial determinations of sKL-6 may be of prognostic use.References:[1]Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. 5.[2]Tian W, Jiang W, Yao J, Nicholson CJ, Li RH, Sigurslid HH, et al. Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Med Virol. 2020.[3]Wang D, Li R, Wang J, Jiang Q, Gao C, Yang J, et al. Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect Dis. 2020;20(1):519.Disclosure of Interests:None declared.

scholarly journals Intra-tumoral molecular heterogeneity in benign and malignant pheochromocytomas and extra-adrenal sympathetic paragangliomas

2010 ◽  
Vol 17 (3) ◽  
pp. 653-662 ◽  
Author(s):  
Esther Korpershoek ◽  
Claudia K Stobbe ◽  
Francien H van Nederveen ◽  
Ronald R de Krijger ◽  
Winand N M Dinjens
Keyword(s):  
Multiple Endocrine Neoplasia Type ◽  
Malignant Tumors ◽  
Germline Mutations ◽  
Benign Tumors ◽  
Molecular Heterogeneity ◽  
Hereditary Tumor Syndromes ◽  
Molecular Aberrations ◽  
Sporadic Tumors ◽  
Chromosome 1P36

Pheochromocytomas (PCCs) and extra-adrenal sympathetic paragangliomas (sPGLs) are catecholamine-producing tumors occurring in the context of hereditary tumor syndromes, with known germline mutations, and as sporadic tumors. The pathogenesis of sporadic PCC and sPGL is poorly understood, and little is known about intra-tumoral heterogeneity with respect to molecular aberrations. Since knowledge on intra-tumoral heterogeneity is important for understanding the pathogenesis of these tumors, we investigated 12 benign and 8 malignant PCCs and sPGLs for loss of heterozygosity (LOH) on DNA extracted from different regions of each tumor and from metastases. LOH markers were selected on chromosomal regions frequently deleted in PCC, including 1p, 3q, 3p, and 11p. Benign tumors were found to have less intra-tumoral heterogeneity (overall 8%) than malignant tumors (overall 23%), with the highest frequencies for chromosome 1p36 in the benign tumors (17%) and 1p13 and 3q24 in malignant tumors (both 38%). In addition, differences in LOH patterns were detected between paired primary malignant tumors, and their metastases and different LOH patterns were observed in bilateral PCC of a multiple endocrine neoplasia type 2 patient. We demonstrate that malignant PCC and sPGL have more intra-tumoral molecular heterogeneity than benign tumors, which suggests that benign and malignant PCC and sPGL have a different pathogenesis.

THE PROGNOSTIC VALUE OF PD-L1 EXPRESSION IN TUMOR AND IMMUNE CELLS IN SQUAMOUS CELL CARCINOMA OF THE ORAL MUCOSA

2017 ◽  
Vol 63 (5) ◽  
pp. 759-765
Author(s):  
Svetlana Kutukova ◽  
Natalya Belyak ◽  
Grigoriy Raskin ◽  
Marina Mukhina ◽  
Georgiy Manikhas ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Malignant Tumor ◽  
Immune Cells ◽  
Prognostic Value ◽  
Hard Palate ◽  
Malignant Tumors ◽  
Small Cell ◽  
Alveolar Process ◽  
Small Cell Lung ◽  
Lower Jaw

The most frequent of malignant tumor cites of the oral mucosa are tongue - 55 %, mucosa of the cheek - 12 %, the fundus of the oral cavity - 10 %, the alveolar process of the upper jaw and the hard palate - 9 %, the alveolar process of the lower jaw - 6 %, the soft palate - 2 %. Malignant tumor cells carry PD-L1 ligands on their surface and its expression level is often correlated with an unfavorable prognosis in particular for such tumors as melanoma, kidney cancer and non-small cell lung cancer. It is relevant to evaluate the correlation between overexpression of PD-L1 and overall survival in patients with malignant tumors of the oral mucosa.

scholarly journals Retinoblastoma genetics screening and clinical management

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Himika Gupta ◽  
Sivasankar Malaichamy ◽  
Ashwin Mallipatna ◽  
Sakthivel Murugan ◽  
Nallathambi Jeyabalan ◽  
...  
Keyword(s):  
Clinical Management ◽  
Detection Rate ◽  
Mutation Detection ◽  
Gene Mutations ◽  
Disease Recurrence ◽  
Germline Mutations ◽  
Global Studies ◽  
Mutation Detection Rate ◽  
Gene Deletions

Abstract Background India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored. Methods Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence. Results Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy. Conclusions We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.

scholarly journals Glucocorticoid Receptor Beta and Its Prognostic Value on Treatment Response in Chronic Vulvar Dermatitis

2021 ◽  
pp. 1-8
Author(s):  
Valerie Bernays ◽  
Mariusz Pawel Kowalewski ◽  
Ioannis Dedes ◽  
Katrin Kerl French ◽  
Daniel Fink ◽  
...  
Keyword(s):  
Cohort Study ◽  
Glucocorticoid Receptor ◽  
Treatment Response ◽  
Retrospective Cohort ◽  
Prognostic Value ◽  
Biological Data ◽  
Topical Glucocorticoids ◽  
Prevalent Disease ◽  
Glucocorticoid Receptor Beta ◽  
Receptor Beta

<b><i>Background:</i></b> Chronic vulvar dermatitis (CVD) is the most prevalent disease in gynecologic dermatology. The treatment mainly depends on topical glucocorticoids (TGC) but is challenged by insufficient treatment response. On a histological level, the upregulation of the glucocorticoid receptor β (GRβ), an inhibitor of the active glucocorticoid receptor α (GRα), is discussed as mechanism of glucocorticoid insensitivity. <b><i>Objectives:</i></b> To analyze whether the expression of GRβ protein at baseline in keratinocytes may predict responsiveness to TGC in patients with CVD. <b><i>Methods:</i></b> In this retrospective cohort study, clinical and biological data of 25 women with a histological diagnosis of chronic vulvar eczema were analyzed. Randomization was done according to the responsiveness to TGC treatment (responsive vs. nonresponsive). Clinical data and the expression of GRβ in the immunohistochemical stained biopsies were examined. <b><i>Results:</i></b> Fifty-two percent of women with CVD were nonresponsive to TGC. GRβ was abundantly expressed in the cytoplasma of keratinocytes of the vulvar epithelium, but no difference in the level of expression was found among GC responsive and nonresponsive patients in the semiquantitative (<i>p</i> = 0.376) and quantitative analysis (<i>p</i> = 0.894). <b><i>Conclusion:</i></b> GRβ is highly expressed in keratinocytes of the vulvar epidermis affected by CVD, but GRβ expression was not increased in patients nonresponsive to TGC compared to responsive patients. Thus, the failure mechanism in nonresponders still remains to be elucidated.

scholarly journals Lipschütz Ulcer: An Unusual Diagnosis that Should Not be Neglected

2021 ◽  
Vol 43 (05) ◽  
pp. 414-416
Author(s):  
Daniela Alexandra Gonçalves Pereira ◽  
Eliana Patrícia Pereira Teixeira ◽  
Ana Cláudia Martins Lopes ◽  
Ricardo José Pina Sarmento ◽  
Ana Paula Calado Lopes
Keyword(s):  
Emergency Department ◽  
Differential Diagnosis ◽  
Clinical Course ◽  
Malignant Tumors ◽  
Sudden Onset ◽  
Drug Reactions ◽  
Genital Ulceration ◽  
Sexually Transmitted ◽  
Inflammatory Processes ◽  
Genital Ulcers

AbstractThe diagnosis of genital ulcers remains a challenge in clinical practice. Lipschütz ulcer is a non-sexually transmitted rare and, probably, underdiagnosed condition, characterized by the sudden onset of vulvar edema along with painful necrotic ulcerations. Despite its unknown incidence, this seems to be an uncommon entity, with sparse cases reported in the literature. We report the case of an 11-year-old girl who presented at the emergency department with vulvar ulcers. She denied any sexual intercourse. The investigation excluded sexually transmitted infections, so, knowledge of different etiologies of non-venereal ulcers became essential. The differential diagnoses are extensive and include inflammatory processes, drug reactions, trauma, and malignant tumors. Lipschütz ulcer is a diagnosis of exclusion. With the presentation of this case report, the authors aim to describe the etiology, clinical course, and outcomes of this rare disease, to allow differential diagnosis of genital ulceration.

scholarly journals Association between home insulation and hospital admission rates: retrospective cohort study using linked data from a national intervention programme

BMJ ◽  
2020 ◽  
pp. m4571 ◽  
Author(s):  
Caroline Fyfe ◽  
Lucy Telfar ◽  
Barnard ◽  
Philippa Howden-Chapman ◽  
Jeroen Douwes
Keyword(s):  
Cohort Study ◽  
Heart Disease ◽  
Confidence Interval ◽  
Hospital Admission ◽  
Retrospective Cohort ◽  
Rate Ratio ◽  
Hospital Admissions ◽  
Relative Rate ◽  
Intervention Programme ◽  
Admission Rates

Abstract Objectives To investigate whether retrofitting insulation into homes can reduce cold associated hospital admission rates among residents and to identify whether the effect varies between different groups within the population and by type of insulation. Design A quasi-experimental retrospective cohort study using linked datasets to evaluate a national intervention programme. Participants 994 317 residents of 204 405 houses who received an insulation subsidy through the Energy Efficiency and Conservation Authority Warm-up New Zealand: Heat Smart retrofit programme between July 2009 and June 2014. Main outcome measure A difference-in-difference approach was used to compare the change in hospital admissions of the study population post-insulation with the change in hospital admissions of the control population that did not receive the intervention over the same two timeframes. Relative rate ratios were used to compare the two groups. Results 234 873 hospital admissions occurred during the study period. Hospital admission rates after the intervention increased in the intervention and control groups for all population categories and conditions with the exception of acute hospital admissions among Pacific Peoples (rate ratio 0.94, 95% confidence interval 0.90 to 0.98), asthma (0.92, 0.86 to 0.99), cardiovascular disease (0.90, 0.88 to 0.93), and ischaemic heart disease for adults older than 65 years (0.79, 0.74 to 0.84). Post-intervention increases were, however, significantly lower (11%) in the intervention group compared with the control group (relative rate ratio 0.89, 95% confidence interval 0.88 to 0.90), representing 9.26 (95% confidence interval 9.05 to 9.47) fewer hospital admissions per 1000 in the intervention population. Effects were more pronounced for respiratory disease (0.85, 0.81 to 0.90), asthma in all age groups (0.80, 0.70 to 0.90), and ischaemic heart disease in those older than 65 years (0.75, 0.66 to 0.83). Conclusion This study showed that a national home insulation intervention was associated with reduced hospital admissions, supporting previous research, which found an improvement in self-reported health.

scholarly journals High Diagnostic and Prognostic Value of Steroidogenic Factor-1 Expression in Adrenal Tumors

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 4066-4066
Author(s):  
Silviu Sbiera ◽  
Sebastian Schmull ◽  
Guillaume Assie ◽  
Hans-Ullrich Voelker ◽  
Luitgard Kraus ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Adrenal Tumors ◽  
Steroidogenic Factor 1 ◽  
Diagnostic And Prognostic Value
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