| 1. |
- Pfeiffer, D., et al.
(författare)
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Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke
- 2019
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 50:2, s. 298-304
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods-Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/ GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of = 3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results-The study sample comprised 816 CADISP patients (age 44.2 +/- 10.3 years) and 2498 SiGN/GISCOME patients (age 67.7 +/- 14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions-Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.
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| 2. |
- Vander Poorten, V., et al.
(författare)
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Polymorphous adenocarcinoma of the salivary glands: reappraisal and update
- 2018
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Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 275:7, s. 1681-1695
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Tidskriftsartikel (refereegranskat)abstract
- Although relatively rare, polymorphous adenocarcinoma (PAC) is likely the second most common malignancy of the minor salivary glands (MiSG). The diagnosis is mainly based on an incisional biopsy. The optimal treatment comprises wide surgical excision, often with adjuvant radiotherapy. In general, PAC has a good prognosis. Previously, PAC was referred to as polymorphous low-grade adenocarcinoma (PLGA), but the new WHO classification of salivary gland tumours has also included under the PAC subheading, the so-called cribriform adenocarcinoma of minor salivary glands (CAMSG). This approach raised controversy, predominantly because of possible differences in clinical behaviour. For example, PLGA (PAC, classical variant) only rarely metastasizes, whereas CAMSG often shows metastases to the neck lymph nodes. Given the controversy, this review reappraises the definition, epidemiology, clinical presentation, diagnostic work-up, genetics, treatment modalities, and prognosis of PAC of the salivary glands with a particular focus on contrasting differences with CAMSG.
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| 3. |
- Bell, D., et al.
(författare)
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Neuroendocrine neoplasms of the sinonasal region
- 2016
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Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074. ; 38:S1, s. E2259-E2266
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Tidskriftsartikel (refereegranskat)abstract
- Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small-cell and large-cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high-grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined.
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| 4. |
- Bishop, J. A., et al.
(författare)
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Rhabdomyoblastic Differentiation in Head and Neck Malignancies Other Than Rhabdomyosarcoma
- 2015
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Ingår i: Head and Neck Pathology. - : Springer Science and Business Media LLC. - 1936-055X .- 1936-0568. ; 9:4, s. 507-518
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Tidskriftsartikel (refereegranskat)abstract
- Rhabdomyosarcoma is a relatively common soft tissue sarcoma that frequently affects children and adolescents and may involve the head and neck. Rhabdomyosarcoma is defined by skeletal muscle differentiation which can be suggested by routine histology and confirmed by immunohistochemistry for the skeletal muscle-specific markers myogenin or myoD1. At the same time, it must be remembered that when it comes to head and neck malignancies, skeletal muscle differentiation is not limited to rhabdomyosarcoma. A lack of awareness of this phenomenon could lead to misdiagnosis and, subsequently, inappropriate therapeutic interventions. This review focuses on malignant neoplasms of the head and neck other than rhabdomyosarcoma that may exhibit rhabdomyoblastic differentiation, with an emphasis on strategies to resolve the diagnostic dilemmas these tumors may present. Axiomatically, no primary central nervous system tumors will be discussed. © 2015, Springer Science+Business Media New York.
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| 5. |
- Hellquist, H., et al.
(författare)
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Development of head and neck pathology in Europe
- 2022
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 480:5, s. 951-965
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Tidskriftsartikel (refereegranskat)abstract
- This review gives a brief history of the development of head and neck pathology in Europe from a humble beginning in the 1930s to the explosive activities the last 15 years. During the decades before the introduction of immunohistochemistry in the 1980s, head and neck pathology grew as a subspeciality in many European countries. In the late 1940s, the Institute of Laryngology and Otology with its own pathology laboratory was founded in London, and in 1964 the World Health Organization (WHO) International Reference Centre for the Histological Classification of Salivary Tumours was established at the Bland-Sutton Institute of Pathology, also in London. International collaboration, and very much so in Europe, led to the publication of the first WHO Classification of Salivary Gland Tumours in 1972. In the 1960s, a salivary gland register was organised in Hamburg and in Cologne the microlaryngoscopy was invented enabling microscopic endoscopic examination and rather shortly afterwards a carbon dioxide laser attached to the microscope became established and laryngeal lesions could be treated by laser vaporisation. During the last three decades, the use of immunohistochemistry supplemented with cytogenetic and refined molecular techniques has greatly facilitated the pathological diagnostics of head and neck lesions and has had a huge impact on research. Collaboration between different European centres has drastically increased partly due to establishment of scientific societies such as the Head and Neck Working Group (HNWG) within the European Society of Pathology and the International Head and Neck Scientific Group (IHNSG). A very large number of European pathologists have contributed to the 2nd, 3rd and 4th WHO books, and are involved in the upcoming 5th edition. Accredited educational meetings and courses are nowadays regularly arranged in Europe. Numerous textbooks on head and neck pathology have been written and edited by European pathologists. The increased collaboration has created larger series of tumours for research and new entities, mainly defined by their genetic abnormalities, are continuously emerging from Europe, particularly regarding salivary gland neoplasms and "undifferentiated" sinonasal tumours. These findings have led to a better and more precise classification and open the possibilities for new treatment strategies.
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| 6. |
- Hugosson, Jonas, 1955, et al.
(författare)
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A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 76:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Background: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality. Objective: To determine whether PSA screening decreases PCa mortality for up to 16 yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended. Design, setting, and participants: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182 160 men, followed up until 2014 (maximum of 16 yr), with a predefined core age group of 162 389 men (55-69 yr), selected from population registry. Outcome measurements and statistical analysis: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended. Results and limitations: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p < 0.001) at 16 yr. The difference in absolute PCa mortality increased from 0.14% at 13 yr to 0.18% at 16 yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16 yr compared with 742 at 13 yr. The number needed to diagnose was reduced to 18 from 26 at 13 yr. Men with PCa detected during the first round had a higher prevalence of PSA >20 ng/ml (9.9% compared with 4.1% in the second round, p < 0.001) and higher PCa mortality (hazard ratio = 1.86, p < 0.001) than those detected subsequently. Conclusions: Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level. Patient summary: In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer. (C) 2019 Published by Elsevier B.V. on behalf of European Association of Urology.
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| 7. |
- Hunt, J. L., et al.
(författare)
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Well-differentiated Neuroendocrine Carcinoma of the Larynx: Confusion of Terminology and Uncertainty of Early Studies
- 2019
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Ingår i: Advances in Anatomic Pathology. - : Ovid Technologies (Wolters Kluwer Health). - 1072-4109. ; 26:4, s. 246-250
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Tidskriftsartikel (refereegranskat)abstract
- Well-differentiated neuroendocrine carcinoma (also known as "carcinoid") of the larynx is an exceedingly rare tumor that has an epithelial origin. These tumors are malignant and have a low, but definite, risk of metastasis. Although it can be challenging, this tumor should be differentiated from moderately differentiated neuroendocrine carcinoma (also known as "atypical carcinoid"). The clinical and pathologic features of this tumor, as well as treatment and prognosis, are reviewed in detail.
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| 8. |
- Rodrigo, J. P., et al.
(författare)
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Neutrophil to Lymphocyte Ratio in Oropharyngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:3
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Forskningsöversikt (refereegranskat)abstract
- Simple Summary Neutrophil-to-lymphocyte ratio (NLR) in peripheral blood samples has been associated with prognosis in several cancers, including head and neck cancer, but in oropharyngeal carcinomas its prognostic value, especially in relation to human papillomavirus (HPV) infection, has been little studied. This meta-analysis, including studies on the prognostic value of NLR in oropharyngeal carcinoma, shows that an elevated pretreatment NLR is associated with a worse prognosis in oropharyngeal cancer, regardless of the type of treatment performed, but this prognostic value appears to be specific to HPV-positive oropharyngeal carcinomas. NLR could be used as an affordable prognostic marker in this type of cancer. Neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in various cancers, including head and neck cancer. However, there is limited information on its role in oropharyngeal squamous cell carcinomas (OPSCC) according to HPV status. This prompted the present meta-analysis. Studies were selected when the prognostic value of NLR prior to treatment was evaluated in OPSCC patients, the cutoff value of NLR was available, and the prognostic value of NLR was evaluated by time-to-event survival analysis. A total of 14 out of 492 articles, including 7647 patients, were analyzed. The results showed a worse prognosis for the patients with a high NLR: The combined hazard ratios (HR) for overall survival (OS) in patients with an elevated NLR was 1.56 (95% confidence interval (CI) 1.21-2.02; p = 0.0006), for disease-free survival was 1.52 (95% CI 1.34-1.73; p < 0.00001), and for recurrence-free survival was 1.86 (95% CI 1.50-2.30; p < 0.00001). This worse prognosis of high NLR was exclusive of HPV-positive patients: HR for OS in the HPV-positive subgroup was 4.05 (95% CI 1.90-8.62 (p = 0.0003), and in the HPV-negative subgroup 0.92 (95% CI 0.47-1.80; p = 0.82). The prognosis of NLR was not influenced by treatment: The HR for OS for patients treated with radiotherapy/chemoradiotherapy (RT/CRT) was 1.48 (95% CI 1.09-2.01; p = 0.01), and for patients treated with surgery (+/- RT/CRT) was 1.72 (95% CI 1.08-2.72; p = 0.02). In conclusion, an elevated NLR relates to worse outcomes in patients with HPV-positive OPSCC.
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| 9. |
- Skalova, A., et al.
(författare)
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High-grade Transformation/Dedifferentiation in Salivary Gland Carcinomas: Occurrence Across Subtypes and Clinical Significance
- 2021
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Ingår i: Advances in anatomic pathology. - 1533-4031. ; 28:3, s. 107-118
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Tidskriftsartikel (refereegranskat)abstract
- High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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| 10. |
- Watts, Eleanor L., et al.
(författare)
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Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.Methods: Statistical analyses of individual participant data from 12,330 male controls aged 25–85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.Results: Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.Conclusion: Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.
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