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2.
Orv Hetil ; 160(36): 1417-1425, 2019 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-31492087

RESUMO

Introduction: Twenty-five percent of fine-needle aspiration biopsy samples of thyroid nodules produce indeterminate cytological results. Genetic testing of nodules can contribute to accurate diagnosis. Aim: Developing the first gene panel in Europe utilizing the 23 most relevant thyroid oncogenes with 568 mutations. Method: Examination of the isolated DNA from biopsy samples by Ion Torrent new generation sequencing. Results: The validation of our method was performed on tumor tissue samples, in which 127 genetic variations were identified, yet unknown in thyroid tumors. AXIN1 was the most polymorphic gene, while BRAF c.1799T>A (V600E) was the most frequently identified mutation. We detected 36 clinically relevant variants, 75% of which have not been described in the literature. Six of our 8 cytologically malignant and 8 of our 14 indeterminate as well as 20 of our 28 cytologically benign samples were identified as containing pathologic variants in a driver gene (BRAF c.1799T>A, NRAS c.181C>A). Conclusion: We have developed a validated, reliable new generation sequencing-based method with high positive predictive value (89%) and sensitivity (79%), suitable for the early detection of malignant lesions in the thyroid. Orv Hetil. 2019; 160(36): 1417-1425.


Assuntos
Testes Genéticos/métodos , Patologia Molecular/métodos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/genética , Biópsia por Agulha Fina/métodos , Análise Mutacional de DNA , Europa (Continente) , Humanos , Mutação , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/patologia
3.
J Clin Pathol ; 72(11): 725-735, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31395625

RESUMO

Neurodegenerative diseases are characterised by selective dysfunction and progressive loss of synapses and neurons associated with pathologically altered proteins that deposit primarily in the human brain and spinal cord. Recent discoveries have identified a spectrum of distinct immunohistochemically and biochemically detectable proteins, which serve as a basis for protein-based disease classification. Diagnostic criteria have been updated and disease staging procedures have been proposed. These are based on novel concepts which recognise that (1) most of these proteins follow a sequential distribution pattern in the brain suggesting a seeding mechanism and cell-to-cell propagation; (2) some of the neurodegeneration-associated proteins can be detected in peripheral organs; and (3) concomitant presence of neurodegeneration-associated proteins is more the rule than the exception. These concepts, together with the fact that the clinical symptoms do not unequivocally reflect the molecular pathological background, place the neuropathological examination at the centre of requirements for an accurate diagnosis. The need for quality control in biomarker development, clinical and neuroimaging studies, and evaluation of therapy trials, as well as an increasing demand for the general public to better understand human brain disorders, underlines the importance for a renaissance of postmortem neuropathological studies at this time. This review summarises recent advances in neuropathological diagnosis and reports novel aspects of relevance for general pathological practice.


Assuntos
Proteínas do Tecido Nervoso/metabolismo , Sistema Nervoso/metabolismo , Doenças Neurodegenerativas/metabolismo , Patologia Molecular/métodos , Biomarcadores/metabolismo , Biópsia , Humanos , Imuno-Histoquímica , Sistema Nervoso/patologia , Doenças Neurodegenerativas/classificação , Doenças Neurodegenerativas/patologia , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes
4.
PLoS Negl Trop Dis ; 13(8): e0007599, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31386662

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) in Brazil is a neglected, vector-borne, tropical parasitic disease that is responsible for several thousand human deaths every year. The transmission route involves sand flies becoming infected after feeding on infected reservoir host, mainly dogs, and then transmitting the Leishmania infantum parasites while feeding on humans. A major component of the VL control effort is the identification and euthanasia of infected dogs to remove them as a source of infection. A rapid, non-invasive, point-of-care device able to differentiate between the odours of infected and uninfected dogs may contribute towards the accurate diagnosis of canine VL. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the headspace volatile chemicals from the hair of two groups of dogs collected in 2017 and 2018 using a bench-top eNose volatile organic chemical analyser. The dogs were categorised as infected or uninfected by PCR analysis of blood samples taken by venepuncture and the number of parasites per ml of blood was calculated for each dog by qPCR analysis. We demonstrated using a robust clustering analysis that the eNose data could be discriminated into infected and uninfected categories with specificity >94% and sensitivity >97%. The eNose device and data analysis were sufficiently sensitive to be able to identify infected dogs even when the Leishmania population in the circulating blood was very low. CONCLUSIONS/SIGNIFICANCE: The study illustrates the potential of the eNose to rapidly and accurately identify dogs infected with Le. infantum. Future improvements to eNose analyser sensor sensitivity, sampling methodology and portability suggest that this approach could significantly improve the diagnosis of VL infected dogs in Brazil with additional potential for effective diagnosis of VL in humans as well as for the diagnosis of other parasitic diseases.


Assuntos
Doenças do Cão/diagnóstico , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/veterinária , Óxido Nítrico Sintase Tipo III/análise , Patologia Molecular/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Animais , Animais Domésticos/parasitologia , Brasil/epidemiologia , DNA de Protozoário/análise , Doenças do Cão/sangue , Doenças do Cão/epidemiologia , Cães , Leishmania infantum/genética , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Psychodidae/parasitologia , Sensibilidade e Especificidade
5.
Clin Chim Acta ; 498: 47-51, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31430440

RESUMO

Pancreatic cancer is one of the deadliest cancers having an exceptionally high mortality rate. Despite a relatively low incidence (10th among cancers), it is the fourth leading cause of cancer-related deaths in most developed countries. Improving early diagnosis of pancreatic cancer and strengthening the standardised comprehensive treatment remain the main focus of pancreatic cancer research. Tumor markers are usually tumor-associated proteins of clinical relevance in these patients. Although tumor markers carbohydrate antigen (CA 19-9) and carcino-embryonic antigen (CEA) are commonly used, neither demonstrate high diagnostic accuracy. Recently, hematopoietic growth factors (HGFs) and various enzymes have been reported as potential biomarkers for pancreatic cancer. These include macrophage-colony stimulating factor (M-CSF) and granulocyte-colony stimulating factor (G-CSF), interleukin-3 (IL-3), macrophage inhibitory cytokine (MIC-1) and various enzymes (alcohol dehydrogenase, aldehyde dehydrogenase, lysosomal exoglycosidases). With the development of molecular technology, detecting K-ras mutation in serum via polymerase chain reaction (PCR) is becoming more common and efficient. Because K-ras mutation rates are high in many cancers, some regard it as a potential tumor marker. Others have shown the value of serum miRNAs in detection of pancreatic cancer. Unfortunately, there are currently no effective methods of sufficient diagnostic accuracy to detect early-stage surgically resectable pancreatic cancer. In this article we highlight these biomarkers and summarise recent developments in the diagnosis and treatment of pancreatic cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias Pancreáticas/diagnóstico , Patologia Molecular/métodos , Animais , Genes ras/genética , Humanos , Mutação , Neoplasias Pancreáticas/terapia , Patologia Molecular/tendências , Reação em Cadeia da Polimerase
6.
PLoS Negl Trop Dis ; 13(8): e0007056, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31465459

RESUMO

Mycetoma is a devastating neglected tropical disease, caused by various fungal and bacterial pathogens. Correct diagnosis to the species level is mandatory for proper treatment. In endemic areas, various diagnostic tests and techniques are in use to achieve that, and that includes grain culture, surgical biopsy histopathological examination, fine needle aspiration cytological (FNAC) examination and in certain centres molecular diagnosis such as PCR. In this retrospective study, the sensitivity, specificity and diagnostic accuracy of grain culture, surgical biopsy histopathological examination and FNAC to identify the mycetoma causative organisms were determined. The histopathological examination appeared to have better sensitivity and specificity. The histological examination results were correct in 714 (97.5%) out of 750 patients infected with Madurella mycetomatis, in 133 (93.6%) out of 142 patients infected with Streptomyces somaliensis, in 53 (74.6%) out of 71 patients infected with Actinomadura madurae and in 12 (75%) out of 16 patients infected with Actinomadura pelletierii. FNAC results were correct in 604 (80.5%) out of 750 patients with Madurella mycetomatis eumycetoma, in 50 (37.5%) out of 133 Streptomyces somaliensis patients, 43 (60.5%) out of 71 Actinomadura madurae patients and 11 (68.7%) out of 16 Actinomadura pelletierii. The mean time required to obtain the FNAC result was one day, and for the histopathological examinations results it was 3.5 days, and for grain it was a mean of 16 days. In conclusion, histopathological examination and FNAC are more practical techniques for rapid species identification than grain culture in many endemic regions.


Assuntos
Testes Diagnósticos de Rotina/métodos , Micetoma/diagnóstico , Micetoma/microbiologia , Micetoma/patologia , Patologia Molecular/métodos , Actinobacteria/isolamento & purificação , Adolescente , Adulto , Idoso , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Madurella/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Micetoma/cirurgia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Sensibilidade e Especificidade , Streptomyces/isolamento & purificação , Adulto Jovem
7.
Hemoglobin ; 43(2): 145-147, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31268351

RESUMO

More than 900 abnormal hemoglobin (Hb) ß chain variants have now been characterized. The majority are due to point mutations resulting in a single amino acid substitution within the globin gene involved, with nearly twice as many ß chain variants identified compared to α chain variants. Although most of these variants are clinically and hematologically silent, they can interact with different thalassemia mutations, which could sometimes render laboratory diagnostics in a routine setting difficult. In this study, we present a case of coinheritance of Hb City of Hope [ß69(E13)Gly→Ser; HBB: c.208G>A] and ß-thalassemia (ß-thal), that compromises the molecular diagnosis of ß-thal trait.


Assuntos
Códon/genética , Hemoglobinas Anormais/genética , Mutagênese Insercional , Patologia Molecular/métodos , Globinas beta/genética , Talassemia beta/diagnóstico , Hemoglobinopatias/genética , Heterozigoto , Humanos
8.
Int J Technol Assess Health Care ; 35(4): 327-333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31292015

RESUMO

OBJECTIVES: The cost-effectiveness of molecular pathology testing is highly context dependent. The field is fast-moving, and national health technology assessment may not be relevant or timely for local decision makers. This study illustrates a method of context-specific economic evaluation that can be carried out in a limited timescale without extensive resources. METHODS: We established a multi-disciplinary group including an oncologist, pathologists and a health economist. We set out diagnostic and treatment pathways and costs using registry data, health technology assessments, guidelines, audit data, and estimates from the group. Sensitivity analysis varied input parameters across plausible ranges. The evaluation setting was the West of Scotland and UK NHS perspective was adopted. The evaluation was assessed against the AdHopHTA checklist for hospital-based health technology assessment. RESULTS: A context-specific economic evaluation could be carried out on a timely basis using limited resources. The evaluation met all relevant criteria in the AdHopHTA checklist. Health outcomes were expected to be at least equal to the current strategy. Annual cost savings of £637,000 were estimated resulting primarily from a reduction in the proportion of patients receiving intravenous infusional chemotherapy regimens. The result was not sensitive to any parameter. The data driving the main cost saving came from a small clinical audit. We recommended this finding was confirmed in a larger population. CONCLUSIONS: The method could be used to evaluate testing changes elsewhere. The results of the case study may be transferable to other jurisdictions where the organization of cancer services is fragmented.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Patologia Molecular/economia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/genética , Análise Custo-Benefício , Humanos , Modelos Econométricos , Metástase Neoplásica , Patologia Molecular/métodos , Anos de Vida Ajustados por Qualidade de Vida , Escócia , Sensibilidade e Especificidade , Medicina Estatal , Avaliação da Tecnologia Biomédica/métodos
9.
Microb Pathog ; 135: 103635, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352064

RESUMO

OBJECTIVES: Mycoplasma hominis (M.hominis) infections are sexually transmitted and usually associated with urogenital and respiratory diseases. The aim of our study was to (i) detect M. hominis in the vaginal and urine samples of sexually active women using three different detection methods and (ii) to determine the antimicrobial susceptibility and recurrence after the treatment. METHODS: Both vaginal and urine samples were collected from 110 sexually active women at the Obstetrics and Gynecology Clinic, Baskent University Ankara Hospital, Turkey, between March 2015 and February 2016. The presence of M. hominis in the vaginal and urine samples was detected by in vitro culture, two biochemical diagnostics kits (Mycoplasma IES (Autobio, China) and Mycoplasma IST-2 (BioMérieux, France) and PCR. The antibiotic susceptibility of each sample was tested using the kits. The women positive for M. hominis were treated either singly or along with their sexual partners by tetracycline. RESULTS: M. hominis was detected in 72 of 220 (32.7%) samples (both vaginal and urine). Of which 37 showed contrary results with two different kits and then were confirmed by PCR. In 13 samples the IES kit identified M. hominis missed by IST-2, and in 8 samples the MIST-2 kit identified M. hominis missed by IES, while both kits missed 6 samples that were agar culture positive for M. hominis." The highest susceptibility rate was observed against pristinamycin (100%), followed by 91%, 83%, and 75% for doxycycline, tetracycline, and josamycin, respectively. Twenty-five patients treated with tetracycline were followed after one month. The recurrence of M. hominis was not observed in any of the 18 cases where both sexual partners were treated but recurred in 5 of the 7 singly treated women. CONCLUSIONS: The rate of M. hominis detection was significantly higher in the vaginal samples compared to the urine samples. The probability of detecting M. hominis by IST-2 kit was 1.18 times less than IES kit (p < 0.001). When the relationship between the samples was examined, the difference between IES and IST-2 for detecting M. hominis was statistically significant (p < 0.01). Antibiotic susceptibility tests indicated that the tetracycline group of antibiotics was effective in eliminating M. hominis when given to both the sexual partners.


Assuntos
Técnicas de Cultura de Células/métodos , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/microbiologia , Mycoplasma hominis/crescimento & desenvolvimento , Mycoplasma hominis/isolamento & purificação , Patologia Molecular/métodos , Antibacterianos/farmacologia , Doxiciclina/farmacologia , Feminino , Hospitais Universitários , Humanos , Josamicina/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma hominis/genética , Obstetrícia , Tetraciclina/farmacologia , Turquia , Vagina/microbiologia
10.
Semin Diagn Pathol ; 36(5): 342-354, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31182318

RESUMO

Molecular diagnostic techniques are part of the ancillary arsenal of anatomic pathologists. Advances in technology and knowledge regarding disease pathogenesis, tumorigenesis, and immune function contribute to the development of these assays. However, each technique, if applied incorrectly or in ignorance, can lead to difficulties in execution or errors in interpretation. In this review of commonly used molecular diagnostic tests, including immunohistochemistry, microsatellite instability testing, chromosomal microarray testing, and conventional and next-generation sequencing, the emphasis will be on potential pitfalls and considerations for each platform. Emerging technologies that may be used in clinical applications in the near future will also be discussed. An understanding of the methodologies, advantages, and drawbacks of molecular assays will help pathologists aid in diagnostic and therapeutic decisions.


Assuntos
Técnicas de Diagnóstico Molecular/métodos , Patologia Molecular/métodos , Humanos
11.
RNA ; 25(9): 1211-1217, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31209064

RESUMO

Facioscapulohumeral muscular dystrophy (FSHD) is among the most common forms of muscular dystrophy. FSHD is caused by aberrant expression of the toxic DUX4 gene in muscle. Detecting endogenous DUX4 in patient tissue using conventional methods can be challenging, due to the low level of DUX4 expression. Therefore, developing simple and trustworthy DUX4 detection methods is an important need in the FSHD field. Here, we describe such a method, which uses the RNAscope assay, an RNA in situ hybridization (ISH) technology. We show that a custom-designed RNAscope assay can detect overexpressed DUX4 mRNA in transfected HEK293 cells and endogenous DUX4 mRNA in FSHD patient-derived myotubes. The RNAscope assay was highly sensitive for tracking reductions in DUX4 mRNA following treatment with our therapeutic mi405 microRNA, suggesting that RNAscope-based DUX4 expression assays could be developed as a prospective outcome measure in therapy trials. This study could set the stage for optimizing and developing a new, rapid RNA ISH-based molecular diagnostic assay for future clinical use in the FSHD field.


Assuntos
Proteínas de Homeodomínio/genética , Hibridização In Situ/métodos , RNA/genética , Linhagem Celular , Perfilação da Expressão Gênica/métodos , Células HEK293 , Humanos , Fibras Musculares Esqueléticas/metabolismo , Distrofia Muscular Facioescapuloumeral/genética , Patologia Molecular/métodos , RNA Mensageiro/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-31187717

RESUMO

BACKGROUND: Several compositions for determination of specific molecular components in allergens have recently been patented. The role of Molecular Allergy (MA) diagnostics in suspected IgE mediated allergic conditions is currently debated. Guideline reports have concluded that population- based studies involving evaluation of the usefulness of MA diagnostics are needed. OBJECTIVE: To evaluate the usefulness of MA diagnostics in a secondary pediatric referral center. METHODS: A total of 961 children and adolescents aged 0.2-18.8 (mean 7.0) years was included in a prospective observational survey. Inclusion criterion was a suspected diagnosis of an IgE mediated condition based on history and clinical symptoms and signs. If a specific diagnosis could not be reached from conventional investigations suspected peanut allergy, birch pollen allergy and associated crossreactivity, insect allergy and triggering allergens for specific immunotherapy were assessed by MA diagnostics. RESULTS: Based on conventional work-up a diagnostic conclusion was established in 946 patients (98.4%). MA diagnostics were performed in 15 individuals (1.6%), 7 girls and 8 boys aged 3.2 to 17.8 (mean 10.6) years. In 8 cases a specific diagnosis was established based on MA diagnostics; in 7 cases MA diagnostics could not improve diagnosis. MA were most frequently (N = 7 (14%)) used in children with peanut allergy (N = 50). CONCLUSION: Most patients in a secondary pediatric referral center with suspected IgE mediated allergy can be managed by conventional diagnostic methods. MA diagnostics may be useful in small and selected subgroups as in patients with suspected peanut allergy, however, may not be helpful in all cases.


Assuntos
Hospitais Pediátricos/estatística & dados numéricos , Hipersensibilidade/diagnóstico , Patologia Molecular/métodos , Adolescente , Criança , Pré-Escolar , Reações Cruzadas , Dinamarca/epidemiologia , Testes Diagnósticos de Rotina , Feminino , Humanos , Hipersensibilidade/epidemiologia , Imunoglobulina E/metabolismo , Lactente , Masculino , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Centros de Cuidados de Saúde Secundários , Inquéritos e Questionários
14.
Histopathology ; 75(3): 312-319, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31054167

RESUMO

AIMS: Results from external quality assessment revealed considerable variation in neoplastic cell percentages (NCP) estimation in samples for biomarker testing. As molecular biology tests require a minimal NCP, overestimations may lead to false negative test results. We aimed to develop recommendations to improve the NCP determination in a prototypical entity - colorectal carcinoma - that can be adapted for other cancer types. METHODS AND RESULTS: A modified Delphi study was conducted to reach consensus by 10 pathologists from 10 countries with experience in determining the NCP for colorectal adenocarcinoma. This study included two online surveys and a decision-making meeting. Consensus was defined a priori as an agreement of > 80%. All pathologists completed both surveys. Consensus was reached for 8 out of 19 and 2 out of 13 questions in the first and second surveys, respectively. Remaining issues were resolved during the meeting. Twenty-four recommendations were formulated. Major recommendations resulted as follows: only pathologists should conduct the morphological evaluation; nevertheless molecular biologists/technicians may estimate the NCP, if specific training has been performed and a pathologist is available for feedback. The estimation should be determined in the area with the highest density of viable neoplastic cells and lowest density of inflammatory cells. Other recommendations concerned: the determination protocol itself, needs for micro- and macro-dissection, reporting and interpreting, referral practices and applicability to other cancer types. CONCLUSION: We believe these recommendations may lead to more accurate NCP estimates, ensuring the correct interpretation of test results, and might help in validating digital algorithms in the future.


Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Oncologia/normas , Patologia Molecular/normas , Adenocarcinoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Consenso , Técnica Delfos , Humanos , Oncologia/métodos , Patologia Molecular/métodos
15.
Medicine (Baltimore) ; 98(20): e15402, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096436

RESUMO

Adenoid cystic carcinoma (ACC) is an uncommon salivary gland malignancy with a poor long-term prognosis. Clinical reports show the high rates of local recurrences and distant metastases. This study aimed to investigate the expression of MIF, Beclin1, and light-chain 3 (LC3) in salivary adenoid cystic carcinoma (SACC).Tissue specimens were obtained from 48 salivary glands adenoid cystic carcinoma (SACC) patients and 15 oral squamous cell carcinoma (OSCC) patients. Immunohistochemical staining was performed to estimate the level of LC3, Beclin1, and MIF. All SACC patients were followed up. The Kaplan-Meier method was used to compare the prognosis of patients after treatment.The 3-year, 5 year-, and 10 year-survival rates of the SACC patients were 83.9%, 69.9%, and 46.6%, respectively. MIF, LC3, and Beclin1 in SACC were all obviously over-expressed. MIF showed an increased tendency in cases with advanced TNM stages, and at the same time, there was an inversely proportional relationship between MIF and LC3, Beclin1.The long-term survival of SACC patients is poor. MIF might be a risk factor for SACC patients, whereas, LC3 and Beclin1 might be an effective strategy for treatment of SACC.


Assuntos
Proteína Beclina-1/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Patologia Molecular/métodos , Neoplasias das Glândulas Salivares/metabolismo , Adulto , Idoso , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias/métodos , Prognóstico , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia , Taxa de Sobrevida
16.
Urologe A ; 58(7): 747-751, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31049636

RESUMO

Besides evidence- and guideline-based tumor therapy, personalized targeted therapies within study settings or individual experimental settings in advanced cancers without further therapeutic options are emerging. A comprehensive molecular analysis of the tumor in a molecular pathology laboratory is important for all targeted therapy approaches. However, the interpretation of the molecular results is crucial and potential therapeutic conclusions can only be drawn by considering the clinical situation and within a setting of oncological experience. Therefore, the molecular results and their potential impact have to be discussed at a molecular tumor board, an interdisciplinary expert team consisting of clinicians, oncologists, (molecular) pathologists, systems physicians, study teams and where required geneticists. If the molecular tumor board decides a targeted therapeutic approach is appropriate, patients should be enrolled in studies or registries with controlled settings and documentation in order to evaluate the therapeutic concepts. Furthermore, molecular-based individual experimental therapies are possible within extreme clinical situations.


Assuntos
Terapia de Alvo Molecular , Neoplasias/genética , Patologistas , Patologia Molecular , Neoplasias Urológicas , Urologistas , Testes Genéticos , Humanos , Pesquisa Interdisciplinar , Patologia Molecular/métodos , Equipe de Assistência ao Paciente , Medicina de Precisão/métodos
17.
Transplant Proc ; 51(3): 729-733, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30979457

RESUMO

BACKGROUND: TruGraf v1 is a well-validated DNA microarray-based test that analyzes blood gene expression profiles as an indicator of immune status in kidney transplant recipients with stable renal function. METHODS: In this study, investigators assessed clinical utility of the TruGraf test in patient management. In a retrospective study, simultaneous blood tests and clinical assessments were performed in 192 patients at 7 transplant centers, and in a prospective observational study they were performed in 45 subjects at 5 transplant centers. RESULTS: When queried regarding whether or not the TruGraf test result impacted their decision regarding patient management, in 168 of 192 (87.5%) cases the investigator responded affirmatively. The prospective study indicated that TruGraf results supported physicians' decisions on patient management 87% (39/45) of the time, and in 93% of cases physicians indicated that they would use serial TruGraf testing in future patient management. A total of 21 of 39 (54%) reported results confirmed their decision that no intervention was needed, and 17 of 39 (44%) reported that results specifically informed them that a decision not to perform a surveillance biopsy was correct. CONCLUSIONS: TruGraf is the first and only noninvasive test to be evaluated for clinical utility in determining rejection status of patients with stable renal function and shows promise of providing support for clinical decisions to avoid unnecessary surveillance biopsies with a high degree of confidence. TruGraf is an invaluable addition to the transplant physician's tool kit for managing patient health by avoiding painful and invasive biopsies, reducing health care costs, and enabling frequent assessment of patients with stable renal function to confirm immune quiescence.


Assuntos
Perfilação da Expressão Gênica/métodos , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Biópsia , Tomada de Decisões , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Patologia Molecular/métodos , Médicos , Estudos Prospectivos , Estudos Retrospectivos
18.
Virchows Arch ; 475(1): 3-11, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30877381

RESUMO

In recent years, cytopathology has established itself as an independent diagnostic modality to guide clinical management in many different settings. The application of molecular techniques to cytological samples to identify prognostic and predictive biomarkers has played a crucial role in achieving this goal. While earlier studies have demonstrated that single biomarker testing is feasible on cytological samples, currently, this provides only limited and increasingly insufficient information in an era where an increasing number of biomarkers are required to guide patient care. More recently, multigene mutational assays, such as next-generation sequencing (NGS), have gained popularity because of their ability to provide genomic information on multiple genes. The cytopathologist plays a key role in ensuring success of NGS in cytological samples by influencing the pre-analytical steps, optimizing preparation types and adequacy requirement in terms of cellularity and tumor fraction, and ensuring optimal nucleic acid extraction for DNA input requirements. General principles of the role and potential of NGS in molecular cytopathology in the universal healthcare (UHC) European environment and examples of principal clinical applications were discussed in the workshop that took place at the 30th European Congress of Pathology in Bilbao, European Society of Pathology, whose content is here comprehensively described.


Assuntos
Marcadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Patologia Molecular/métodos , Medicina de Precisão/métodos , Congressos como Assunto , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Manejo de Espécimes , Transcriptoma
19.
Endocr Pathol ; 30(2): 134-137, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30825100

RESUMO

Molecular tests and mutational panels such as Afirma Gene Expression Classifier (GEC) and ThyroSeq, respectively, have been used to help risk stratify cytologically indeterminate thyroid nodules with the aim to reduce unnecessary surgeries. We studied the effect of molecular testing on the rate of surgical resection in these nodules. Thyroid nodules with indeterminate (Bethesda III/IV) cytology that underwent molecular testing (GEC or ThyroSeq) at our institution between June 2012 and August 2016 were retrospectively reviewed. We collected demographics, cytology diagnoses, molecular test results, and whether surgical resection was performed. Two hundred eighty-three nodules met inclusion criteria: 202 nodules tested with GEC and 81 tested with ThyroSeq. In the cohort of GEC-tested nodules, 99/202 (49%) yielded "suspicious" and 103/202 (51%) yielded "benign" results, with an overall resection rate of 70/99 (71%) in "suspicious" versus 13/103 (13%) in "benign" nodules. In the cohort of ThyroSeq-tested nodules, 13/81 (16%) of nodules yielded a "high-risk mutation" and 68/81 (84%) of nodules yielded "no high-risk mutation," with overall resection rates of 11/13 (85%) and 30/68 (44%), respectively. Rates of resection were higher for Bethesda IV than for III nodules, regardless of molecular results. For both GEC and ThyroSeq, molecular test results seemed to correlate with the rate of resection at our institution. Rates of resection for cytologically indeterminate nodules that were "benign" or "no high-risk mutation" appeared to differ from those that were "suspicious" or "high-risk mutation" on molecular panel testing by GEC and ThyroSeq, respectively. Our findings support that molecular test results are impacting management.


Assuntos
Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Biópsia por Agulha Fina , Estudos de Coortes , Humanos , Mutação/genética , Resultados Negativos , Patologia Molecular/métodos , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
20.
Fetal Pediatr Pathol ; 38(3): 206-214, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30821558

RESUMO

BACKGROUND: Adeno-associated viruses (AAVs) have been found in human blood cells, cervical biopsies, and epithelial cell brushings, endometrium, and abortion material, which suggest their possible roles in the induction of miscarriage. OBJECTIVE: In this case control study, the presence of AAV DNA in placental tissue of spontaneous and therapeutic abortions was compared. METHOD: Placenta samples were evaluated for AAV DNA by hemi-nested PCR in miscarriages occurring in the first 24 weeks of pregnancy from therapeutic and spontaneous abortions. RESULTS: Eighty-one therapeutic abortions (control group) and 83 spontaneous abortions (case group) were evaluated. Sixty-two (38.2%) of 164 abortions were AAV positive, including 35 (21.6%) spontaneous abortions and 27 (16.6%) therapeutic abortions. CONCLUSION: There was no statistically significant difference between the presence of the AAV genome in spontaneous and therapeutic abortions. This observation was consistent with other studies in this area.


Assuntos
Aborto Espontâneo/patologia , DNA/genética , Dependovirus/patogenicidade , Patologia Molecular , Aborto Espontâneo/diagnóstico , Aborto Terapêutico/métodos , Estudos de Casos e Controles , Dependovirus/genética , Feminino , Humanos , Patologia Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Gravidez
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