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In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.
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BACKGROUND: Use of liquid biopsy for minimal invasive follow-up diagnostics of non-small-cell lung carcinomas (NSCLCs). OBJECTIVES: Systematic search for new putative blood-based hypermethylation biomarkers to discriminate NSCLC patients from patients without a malign disease. METHODS: Quantitative analysis of gene promoter DNA methylation of potential biomarkers from cfDNA (plasma) with pyrosequencing. RESULTS: cfDNA hypermethylation in plasma confirmed significant higher methylation frequencies of the candidate gene CFTR of the NSCLC patients compared to the combined control groups and to NSCLC patients after curative therapy of primary NSCLC (post-NSCLC). ROC-analysis of the best discriminatory CpGs of the CFTR promotor (CpG1-2-4) revealed a sensitivity of 52% in NSCLC patients and a specificity of 90% in the post-NSCLC group (AUC: 0.69; pâ¯< 0.05). CONCLUSIONS: Promotor hypermethylation of the potential biomarker CFTR shows a discriminatory potential for differentiation of NSCLC patients to patients without a malign disease and should further be investigated.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Metilación de ADN , Humanos , Biopsia Líquida , Regiones Promotoras GenéticasRESUMEN
BACKGROUND: Fetal autopsy rates are decreasing in Western countries although post-mortem examinations render important information for the parents concerning the cause of abortion and risk of recurrence in future pregnancies. OBJECTIVE: The intention of the presented study was to analyze the development of fetal autopsies in Germany during the last decade and to review accessible information obtained by fetal autopsy. MATERIAL AND METHODS: Reports of fetal autopsies conducted in two German university Institutes of pathology between 2005 and 2014 were evaluated retrospectively. Demographic data and the correlation between clinical diagnoses and autopsy findings were assessed. In addition, differences between spontaneous and induced cases of abortion and differences between the institutes were also documented. RESULTS: Overall, 428 fetal autopsies were performed, whereby the number of autopsies decreased by 24.2% during the study period. Of the examined fetuses 29.7% were induced abortions which as expected exhibited different malformations compared to cases of spontaneous abortion (p < 0.001). There was no evidence of a malformation or other cause of death in 27.1% of the cases and 95.7% of these abortions occurred spontaneously. A discrepancy between clinical and autopsy findings was evident in 6.8% of cases and 3.5% of the autopsy examinations revealed at least one additional malformation compared to the prenatal clinical data. CONCLUSION: Despite improvements in prenatal diagnostics, fetal autopsies remain an important diagnostic tool even today contributing additional information in a considerable number of cases potentially revising clinical diagnoses.
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Autopsia/estadística & datos numéricos , Anomalías Congénitas/patología , Muerte Fetal/etiología , Enfermedades Fetales/patología , Feto/patología , Aborto Espontáneo/patología , Autopsia/tendencias , Causas de Muerte , Femenino , Alemania , Humanos , Recién Nacido , Embarazo , Prevalencia , Recurrencia , Factores de Riesgo , MortinatoRESUMEN
Autopsies are of key importance for the understanding of the anatomy, pathophysiology and pathomorphology. In forensic medicine, the virtual autopsy is a standard instrument in autopsy practice. The advantage of postmortem imaging is the generation of a three-dimensional pre-autopsy snapshot of the body from head to toe with excellent visualization of skeletal pathologies and air inclusions. When angiography is performed, pathologies of the cardiovascular system can additionally be evaluated. The shortcomings of postmortem imaging are the low soft tissue contrast with CT imaging, the lack of haptic, olfactory and color impressions. Another limitation is the access to CT and particularly to magnetic resonance imaging (MRI) facilities and the necessary experience with the peculiarities of postmortem imaging. To date, postmortem imaging can supplement but not replace the traditional autopsy. Nevertheless, postmortem imaging adds valuable technical capabilities to the traditional autopsy. The ability to achieve valid results for the cause of death and additional diagnoses must be evaluated systematically for postmortem imaging, in particular in addition to CT or MR guided biopsies. This article gives an overview of the current state of the technology and encourages its development for application in pathology departments.
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Autopsia/métodos , Diagnóstico por Imagen , Medicina Legal/métodos , Interfaz Usuario-Computador , Causas de Muerte , Alemania , Humanos , Biopsia Guiada por Imagen , Imagenología Tridimensional , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos XRESUMEN
As even a mere thickening of the urothelium can harbor genetic changes identical to that of low grade papillary urothelial tumors, it is not always possible to clearly recognize a precursor lesion of urothelial carcinoma by routine histological diagnostics. Complementary immunohistochemical and molecular diagnostic methods assist the recognition of these entities. These methods especially help to identify clinically important genetically unstable cells as the hallmark of carcinoma in situ (CIS). Little is known about the clinical significance of the morphological subtypes of CIS, which range from large cell to micropapillary variants. For a better understanding of special types of bladder cancer (e.g. adenocarcinoma and squamous cell carcinoma), it seems to be important to define the phenotype and the molecular pattern of non-urothelial lesions, such as intestinal metaplasia and squamous metaplasia, better and more precisely.
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Carcinoma de Células Transicionales/patología , Lesiones Precancerosas/patología , Neoplasias de la Vejiga Urinaria/patología , Vejiga Urinaria/patología , Urotelio/patología , Adenocarcinoma/clasificación , Adenocarcinoma/genética , Adenocarcinoma/patología , Carcinoma in Situ/clasificación , Carcinoma in Situ/genética , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/clasificación , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Transicionales/clasificación , Carcinoma de Células Transicionales/genética , Transformación Celular Neoplásica/clasificación , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Células Epiteliales/clasificación , Células Epiteliales/patología , Humanos , Hiperplasia/clasificación , Hiperplasia/genética , Hiperplasia/patología , Metaplasia/clasificación , Metaplasia/genética , Metaplasia/patología , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/genética , Neoplasias de la Vejiga Urinaria/clasificación , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
Bladder cancer shows rare variants and special subtypes with diverse prognostic importance and therefore may necessitate different therapeutic approaches. For pathologists it is important to histologically diagnose and specify such variants. Nested variants of urothelial carcinoma with inconspicuous, well-formed tumor cell nests present with an aggressive course. The plasmacytoid variant, which morphologically resembles plasma cells is associated with a shorter survival time and a high frequency of peritoneal metastasis. Micropapillary urothelial carcinoma with small papillary tumor cell islands within artificial tissue retraction spaces and frequent lymphovascular invasion also has a poor prognosis. Other important rare differential variants listed in the World Health Organization (WHO) classification are microcystic, lymphoepithelioma-like, sarcomatoid, giant cell and undifferentiated urothelial carcinomas. Additionally, there are three special types of bladder cancer: squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma of the bladder. These tumors are characterized by pure squamous cell or glandular differentiation and are sometimes less responsive to adjuvant (chemo)therapy. Small cell carcinoma of the bladder mimics the neuroendocrine features of its pulmonary counterpart, shows an aggressive course but is sensitive to (neo-)adjuvant chemotherapy. The morphology and histology of the most important variants and special types are discussed in this review.
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Neoplasias de la Vejiga Urinaria/patología , Adenocarcinoma/clasificación , Adenocarcinoma/patología , Adenocarcinoma/terapia , Carcinoma de Células Pequeñas/clasificación , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Pequeñas/terapia , Carcinoma de Células Escamosas/clasificación , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Transicionales/clasificación , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/terapia , Transformación Celular Neoplásica/patología , Progresión de la Enfermedad , Adhesión a Directriz , Humanos , Invasividad Neoplásica , Pronóstico , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/clasificación , Neoplasias de la Vejiga Urinaria/terapia , Urotelio/patologíaRESUMEN
PURPOSE: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. METHODS: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. RESULTS: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. CONCLUSIONS: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.
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Calicreínas/sangre , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/diagnóstico , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/cirugía , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasia Residual , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Testicular tumors can be divided into germ cell tumors and sex cord stromal tumors. Malignant testicular germ cell tumors (TGCT) represent about 90-95 % of all testicular tumors and are the most common solid neoplasms in young men aged 20-40 years with an increasing incidence in industrialized countries. Treatment of TGCT is performed by an individual and risk-adapted approach taking primary tumor histology, histopathlogical and molecular prognostic risk factors, tumor stage and for metastasized tumors the response to systemic chemotherapy into consideration. Knowledge of the specific histopathology of the primary tumor and the prognostic factors is of utmost importance for the treating urologist and oncologist in order to avoid undertreatment or overtreatment. Established risk factors which have been validated in retrospective and prospective studies for clinical stage I non-seminomatous TGCT are the presence of vascular invasion and the percentage of embryonal carcinoma. In clinical stage I seminomas tumor size (> 4 cm) and presence of rete testis infiltration have been identified as risk factors in retrospective but not in prospective studies. Quantitative histopathology of the primary tumor is also important for the management of small residual masses following chemotherapy: if the masses are ≤ 1 cm, postchemotherapy retroperitoneal lymph node dissection is only indicated if the primary tumor contains ≥ 50 % teratoma. Quantitative pathohistology of the resected residual masses is of importance for the decision-making process of a consolidating chemotherapy which is only of benefit if the amount of vital cancer tissue is > 10 %. Resection of residual hepatic and thoracic masses is indispensable. For gonadal stromal tumors knowledge of atypical nuclear forms, increased rate of mitosis and increased growth fractions are important for therapy planning.
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Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/terapia , Planificación de Atención al Paciente , Neoplasias Testiculares/patología , Neoplasias Testiculares/terapia , Adulto , Antineoplásicos/uso terapéutico , Terapia Combinada , Conducta Cooperativa , Humanos , Comunicación Interdisciplinaria , Escisión del Ganglio Linfático , Masculino , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasia Residual/clasificación , Neoplasia Residual/patología , Neoplasia Residual/terapia , Neoplasias de Células Germinales y Embrionarias/clasificación , Ajuste de Riesgo , Neoplasias Testiculares/clasificación , Testículo/patología , Carga Tumoral , Adulto JovenRESUMEN
Results of molecular pathology have supported changes in the 2004 WHO classification of urothelial cancer. Since then new molecular data such as the distribution pattern of the fibroblast growth factor receptor 3 (FGFR3) has further supported the principle of low and high grade entities of urothelial carcinoma. Animal experiments with knockout mice and conditional knockout systems reveal important parallels to humans and results emphasize the cellular context as a trigger for malignancy. One special feature of the urothelium is its high protection of the urothelial cells by members of the retinoblastoma gene family, efficiently inhibiting invasion even in the presence of p53 mutations. In search of the tumor stem cell phenotype the basal cell phenotype is the focus of attention providing a high clonogenic potential. At the same time detailed analysis of the distribution of mutations in the mitochondrial genome within the urothelium will help to gain insight into the spreading of normal cell or tumor cell clones. The overall data in urological oncology provide evidence that diagnostic and prognostic tools for urothelial cancer can only be reached with multiparametric approaches.
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Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/patología , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Animales , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Cromosomas Humanos Par 19/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Análisis Mutacional de ADN , Genes de Retinoblastoma/genética , Humanos , Ratones , Ratones Noqueados , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Proteínas de Neoplasias/genética , Estadificación de Neoplasias , Células Madre Neoplásicas/patología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Proteína p53 Supresora de Tumor/genética , Urotelio/patologíaRESUMEN
Histological evaluation after biopsy remains the gold standard for the diagnosis of numerous diseases in Internal Medicine. The gastrointestinal tract (e. g. esophagus, liver and large intestine), the kidneys or bone marrow are organs, where biopsy-driven diagnosis and evaluation of therapeutic regimens are of major relevance. Improvement in blood analysis, endoscopic techniques and radiology could significantly reduce the number of biopsies. Hence under certain circumstances, the risk of biopsy can be avoided and non-invasive markers can sufficiently substitute the histological evaluation. However, histological evaluation derived from biopsies remains the standard of diagnosis in many cases in Internal Medicine. In the present review the current standards and future developments of pathologic diagnosis through biopsy are illustrated.
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Biopsia/tendencias , Medicina Interna/tendencias , Patología/tendencias , Diagnóstico Diferencial , HumanosRESUMEN
Urothelial carcinomas include tumors with very different clinical outcomes: 70-80% of urothelial carcinomas are genetically stable and are associated with a favorable prognosis, but 20-30% are genetically unstable and have a high progression rate. Therefore, the current World Health Organization classification (2004) differentiates the histologic grade as low grade (LG) or high grade (HG). Unequivocal language is mandatory to optimize therapy and assess prognosis. In addition to TNM classification and histologic grade, genetic factors such as mutations of p53, fibroblast growth factor receptor 3 (FGFR3), and phosphatidylinositol-3-kinase (PIK(3)CA) are relevant in patients' prognoses.