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1.
World J Urol ; 41(8): 2091-2097, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37528288

RESUMO

PURPOSE: Determining the frequency and distribution of pathogenic germline variants (PGVs) in Austrian prostate cancer (PCa) patients and to assess the accuracy of different clinical risk scores to correctly predict PGVs. METHODS: This cross-sectional study included 313 men with advanced PCa. A comprehensive personal and family history was obtained based on predefined questionnaires. Germline DNA sequencing was performed between 2019 and 2021 irrespective of family history, metastatic or castration status or age at diagnosis. Clinical risk scores for hereditary cancer syndromes were evaluated and a PCa-specific score was developed to assess the presence of PGVs. RESULTS: PGV presence was associated with metastasis (p = 0.047) and castration resistance (p = 0.011), but not with personal cancer history or with relatives with any type of cancer. Clinical risk scores (Manchester score, PREMM5 score, Amsterdam II criteria or Johns Hopkins criteria) showed low sensitivities (3.3-20%) for assessing the probability of PGV presence. A score specifically designed for PCa patients stratifying patients into low- or high-risk regarding PGV probability, correctly classified all PGV carriers as high-risk, whereas a third of PCa patients without PGVs was classified as low risk of the presence of PGVs. CONCLUSION: Application of common clinical risk scores based on family history are not suitable to identify PCa patients with high PGV probabilities. A PCa-specific score stratified PCa patients into low- or high-risk of PGV presence with sufficient accuracy, and germline DNA sequencing may be omitted in patients with a low score. Further studies are needed to evaluate the score.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Estudos Transversais , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fatores de Risco , Células Germinativas/patologia , Áustria , Predisposição Genética para Doença
2.
BMC Gastroenterol ; 21(1): 25, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422007

RESUMO

BACKGROUND: We aimed to determine the prevalence of elevated alanine aminotransferase (eALT) in employees of a German chemical company, and analyze its association with sociodemographic, work- and lifestyle-related factors. METHODS: The cross-sectional study is based on data surveyed from occupational health check-ups between 2013 and 2018 at the site clinic of a chemical company based in Ludwigshafen, Germany. We used logistic regression analyses to assess the association between sociodemographic, work- and lifestyle-related characteristics and eALT. Quantile regression technique was applied to investigate if associations vary across different quantiles of the ALT distribution. RESULTS: Participants (n = 15,348) were predominantly male (78.3%) with a mean age of 42.2 years (SD 10.7). The prevalence of eALT was 18.5% (21.6% in men/7.2% in women) with a geometric mean of 28.9 U/L (32.8 U/L in men/18.5 U/L in women). In the multivariable logistic regression model, odds of eALT were significantly higher for males (OR 2.61; 95%-CI 2.24-3.05), manual workers (OR 1.23; 95%-CI 1.06-1.43), overweight (OR 2.66; 95%-CI 2.36-3.00) or obese respondents (e.g. OR 7.88; 95%-CI 5.75-10.80 for obesity class III), employees who consume any number of alcoholic drinks/week (e.g. OR 1.32; 95%-CI 1.16-1.49 for ≥ 3 drinks per week) and diabetics (OR 1.47; 95%-CI 1.22-1.78). Additionally, season of participation was significantly associated with eALT, with odds being higher for participation in spring, fall or winter, as compared to summer. A significant interaction between age and gender (pInteraction < 0.001) was found, showing approximately a u-shaped age/ALT relationship in women and an inversely u-shaped relationship in men. Quantile regression showed an increasing positive effect of male gender, overweight/obesity, and for diabetics on ALT level when moving from the lowest (q0.1) to the highest (q0.9) considered quantile. Additionally, from the lowest to the highest quantile an increasing negative effect on ALT for older age was observed. CONCLUSIONS: Prevalence of eALT in our sample of employees can be considered as high, with almost one in five participants affected. Identification of risk groups allows the implementation of targeted preventive measures in order to avoid transition to severe morbidity.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Idoso , Alanina Transaminase , Estudos Transversais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Obesidade/epidemiologia , Prevalência , Fatores de Risco
3.
Eur J Prev Cardiol ; 27(7): 682-692, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31569966

RESUMO

Comprehensive stroke care is an interdisciplinary challenge. Close collaboration of cardiologists and stroke physicians is critical to ensure optimum utilisation of short- and long-term care and preventive measures in patients with stroke. Risk factor management is an important strategy that requires cardiologic involvement for primary and secondary stroke prevention. Treatment of stroke generally is led by stroke physicians, yet cardiologists need to be integrated care providers in stroke units to address all cardiovascular aspects of acute stroke care, including arrhythmia management, blood pressure control, elevated levels of cardiac troponins, valvular disease/endocarditis, and the general management of cardiovascular comorbidities. Despite substantial progress in stroke research and clinical care has been achieved, relevant gaps in clinical evidence remain and cause uncertainties in best practice for treatment and prevention of stroke. The Cardiovascular Round Table of the European Society of Cardiology together with the European Society of Cardiology Council on Stroke in cooperation with the European Stroke Organisation and partners from related scientific societies, regulatory authorities and industry conveyed a two-day workshop to discuss current and emerging concepts and apparent gaps in stroke care, including risk factor management, acute diagnostics, treatments and complications, and operational/logistic issues for health care systems and integrated networks. Joint initiatives of cardiologists and stroke physicians are needed in research and clinical care to target unresolved interdisciplinary problems and to promote the best possible outcomes for patients with stroke.


Assuntos
Cardiologia/normas , Doenças Cardiovasculares/terapia , Assistência Integral à Saúde/normas , Prestação Integrada de Cuidados de Saúde/normas , Comunicação Interdisciplinar , Neurologia/normas , Acidente Vascular Cerebral/terapia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Consenso , Comportamento Cooperativo , Humanos , Prognóstico , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia
4.
Allergy Asthma Clin Immunol ; 9(1): 33, 2013 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-24004607

RESUMO

BACKGROUND: Referring to individuals with reactivity to honey bee and Vespula venom in diagnostic tests, the umbrella terms "double sensitization" or "double positivity" cover patients with true clinical double allergy and those allergic to a single venom with asymptomatic sensitization to the other. There is no international consensus on whether immunotherapy regimens should generally include both venoms in double sensitized patients. OBJECTIVE: We investigated the long-term outcome of single venom-based immunotherapy with regard to potential risk factors for treatment failure and specifically compared the risk of relapse in mono sensitized and double sensitized patients. METHODS: Re-sting data were obtained from 635 patients who had completed at least 3 years of immunotherapy between 1988 and 2008. The adequate venom for immunotherapy was selected using an algorithm based on clinical details and the results of diagnostic tests. RESULTS: Of 635 patients, 351 (55.3%) were double sensitized to both venoms. The overall re-exposure rate to Hymenoptera stings during and after immunotherapy was 62.4%; the relapse rate was 7.1% (6.0% in mono sensitized, 7.8% in double sensitized patients). Recurring anaphylaxis was statistically less severe than the index sting reaction (P = 0.004). Double sensitization was not significantly related to relapsing anaphylaxis (P = 0.56), but there was a tendency towards an increased risk of relapse in a subgroup of patients with equal reactivity to both venoms in diagnostic tests (P = 0.15). CONCLUSIONS: Single venom-based immunotherapy over 3 to 5 years effectively and long-lastingly protects the vast majority of both mono sensitized and double sensitized Hymenoptera venom allergic patients. Double venom immunotherapy is indicated in clinically double allergic patients reporting systemic reactions to stings of both Hymenoptera and in those with equal reactivity to both venoms in diagnostic tests who have not reliably identified the culprit stinging insect.

5.
J Neurosurg ; 116(2): 373-84, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21942724

RESUMO

OBJECT: The authors report surgical and endocrinological results of a series of 73 cases of craniopharyngioma that they treated surgically since 1997 to demonstrate their change in treatment strategy and its effect on outcome compared with a previous series and results reported in the literature. METHODS: A total of 73 patients underwent surgery for craniopharyngiomas between May 1997 and January 2005. In patients with poor clinical or neuropsychological condition, even following pretreatment, only stereotactic cyst aspiration took place (8 cases). In the remaining patients, gross-total resection (GTR) was intended and appeared to be possible. The most frequent approaches were subfrontal (27 cases) and transsphenoidal (26 cases); in some cases, a multistep approach was used. The rate of GTR, complications, and functional outcome (comparing pre- and postoperative endocrine and neuropsychological testing) were evaluated. The mean duration of follow-up was 25.2 months. RESULTS: Gross-total resection was achieved in 88.5% of cases in which a transsphenoidal approach was used and 79.5% of those in which a transcranial approach was used (85.2% of those in which a subfrontal approach was used and 72.7% of those in which a frontolateral approach was used). In the total series, GTR was achieved in 83.1% of cases (vs 49.3% in the authors' former series). The complication rate was 13.8% without any mortality. New endocrine deficits were observed more frequently in patients treated with transcranial approaches over the years (16.3%-66.7% vs 2.6%-50.0%) but were less frequent after transsphenoidal approaches (5.2%-19.2% vs 2.9%-45.7%). CONCLUSIONS: Open surgery with intended total resection remains the treatment of choice in most patients. Initial stereotactic cyst aspiration or medical pretreatment to improve the patients' condition and adequate choice of surgical approach(es) are essential to achieve that goal. Nevertheless, a moderate increase in endocrinological deficits has to be accepted. The authors recommend using radiotherapy only in cases in which there are tumor remnants or disease progression after surgery.


Assuntos
Craniofaringioma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Craniofaringioma/patologia , Feminino , Seguimentos , Humanos , Hipopituitarismo/patologia , Hipopituitarismo/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Neoplasias Hipofisárias/patologia , Complicações Pós-Operatórias/terapia , Sucção/métodos , Resultado do Tratamento , Acuidade Visual , Adulto Jovem
6.
Acta Neurochir (Wien) ; 153(7): 1377-90; discussion 1390, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21479997

RESUMO

BACKGROUND: As low-field magnetic resonance imaging (MRI) has very limited significance for intraoperative control of total tumor removal (TTR), we examined the influence of 1.5-T MRI, incorporating higher resolution into the intraoperative strategy of craniopharyngioma surgery. METHODS: Surgery with intraoperative imaging was performed in 25 selected patients in whom tumor resection was anticipated to be difficult according to pre-operative findings. RESULTS: Intraoperative MRI confirmed the intended extent of tumor removal in 15 patients (14 TTRs, one intended incomplete removal, while a second procedure was scheduled due to complex shape). Misinterpretation was false positive or negative in one patient each. The extent of removal was not achieved as expected in eight patients (expectation: seven TTRs, one incomplete removal). In three patients, the expected TTR was achieved by resuming surgery. In another case, that goal was accomplished by performing an unscheduled second procedure. In total, by using intraoperative imaging, the rate of TTR was increased by 16% (four patients), leading to 80% in the entire series. Compared with the literature, the rate of new ophthalmologic and endocrine deficits is acceptable; the rate of other surgical complication is slightly higher but not directly caused by intraoperative imaging. CONCLUSION: Intraoperative 1.5-T MRI provides benefits because of good early prediction of TTR (sensitivity, positive predictive value: 93.8%; specificity, negative predictive value: 88.9%) and a low rate of false-positive results. Moreover, extended resection of remnants visualized is enabled and helps to increase the rate of TTR but does not exclude recurrence.


Assuntos
Craniofaringioma/cirurgia , Hipofisectomia/métodos , Imageamento por Ressonância Magnética/métodos , Monitorização Intraoperatória/métodos , Neoplasias Hipofisárias/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Craniofaringioma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Valor Preditivo dos Testes , Resultado do Tratamento , Adulto Jovem
7.
Neurosurgery ; 67(3): 617-25; discussion 625, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20647974

RESUMO

BACKGROUND: Extensive neurosurgical resection of craniopharyngiomas often requires lifetime hormonal substitution. OBJECTIVE: We investigated the effect of the hormone receptor expression of insulinlike growth factor-1, growth hormone-releasing hormone receptor, growth hormone, progesterone, estrogen (ER-1, ER-beta), and leptins (Ra6.4, Ra12.1, Rb) on tumor recurrence, size, and proliferation using clinical, histopathological, and molecular genetic analysis. PATIENTS AND METHODS: cDNA expression analysis was obtained in a cohort of 20 patients suffering from a craniopharyngioma to systematically determine the expression of above-mentioned receptors. In addition, 51 tumor samples were available to immunohistochemically investigate the extent and distribution of estrogen and progesterone receptors. In 18 tumor specimens, both experimental paradigms could be performed. RESULTS: All hormone receptors under study, including leptins, were detectable in craniopharyngiomas with reverse-transcription polymerase chain reaction but did not reach significance regarding the tested parameters. However, a correlation was observed between tumor size and cell proliferation indexes, as well as with cDNA expression levels of ER-1 and growth hormone receptors. CONCLUSION: The present preliminary data point to a correlation between estrogen and growth hormone receptor expression and proliferation indexes with tumor size in craniopharyngiomas. Because of the small cohort of tumors, these data require expansion and validation. This is the first report about leptin expression in this tumor entity. These findings should prompt careful consideration of hormonal replacement therapy regimens in patients with tumor remnants and evidence of respective receptor expression.


Assuntos
Biomarcadores Tumorais/metabolismo , Craniofaringioma/metabolismo , Hormônios/metabolismo , Neoplasias Hipofisárias/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Criança , Pré-Escolar , Estudos de Coortes , Craniofaringioma/patologia , Craniofaringioma/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/fisiopatologia , Adulto Jovem
8.
Brain Pathol ; 19(3): 357-64, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18540944

RESUMO

Activating beta-catenin (CTNNB1) mutations can be identified in the majority of adamantinomatous craniopharyngiomas (adaCP), suggesting an aberrant Wnt signaling pathway in this histopathologically peculiar tumor entity. However, there is no proven evidence that nuclear translocation of beta-catenin is associated with CTNNB1 mutations and target gene activation. We performed a laser-microdissection-based study comparing beta-catenin accumulating vs. non-accumulating tumor cells. Mutational analysis and gene expression profiling using real-time polymerase chain reaction were conducted in adamantinomatous and papillary tumor specimens. Target gene activation, that is, over-expression of Axin2 could be detected in adaCP, especially in tumor cells with nuclear beta-catenin accumulation. In addition, increased expression of BMP4 was identified in the accumulating cell population, which supports the hypothesis of an oral ectodermal origin. Interestingly, accumulating and non-accumulating tumor cell populations carried CTNNB1 mutations within exon 3. We extended the analysis, therefore, towards genetic regions encoding for membrane linkage and active/passive nuclear transport mechanisms (exon 4 and exon 8-13), but could not detect any alteration. This is the first report demonstrating an association between nuclear beta-catenin accumulation and target gene activation in adaCP. The results confirm the Wnt signaling pathway as molecular basis of the distinct and challenging clinical and morphological phenotype of adaCP.


Assuntos
Craniofaringioma/genética , Transdução de Sinais/fisiologia , Ativação Transcricional , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Adolescente , Adulto , Proteína Axina , Proteína Morfogenética Óssea 4/genética , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Criança , Pré-Escolar , Craniofaringioma/metabolismo , Craniofaringioma/patologia , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Microdissecção , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Wnt/genética
9.
J Neurosurg ; 108(1): 9-18, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18173305

RESUMO

OBJECTIVES: The aim of this paper was to demonstrate the long-term results following microsurgery in a single surgeon's continuous series of patients with Cushing disease (CD), to assess the influence of changes in surgical procedures, and to compare the results with those of other treatment modalities. In particular, preoperative diagnosis, tumor size, results of histological examination, and complications were considered. METHODS: Between 1971 and 2004, 426 patients suffering from newly diagnosed CD underwent primary surgery. Pre-operative measures included clinical examination, endocrinological workup (testing of the hypothalamic-pituitary-adrenal axis, and 2- and 8-mg dexamethasone overnight suppression tests), sellar imaging (polytomography, computed tomography, and magnetic resonance [MR] imaging), and in patients with negative results on imaging studies, inferior petrosal sinus sampling. Follow-up examinations consisting of endocrinological workup, and imaging took place 1 week and 3 months after surgery and then at yearly intervals. RESULTS: During microsurgery as first treatment, the adenoma finding rate was 86.6%. After selective adenomectomy, the remission rate was 75.9%, and this rate showed no improvement over the years. The best results were achieved in microadenomas confirmed on MR imaging or histopathological investigation. The recurrence rate (15%) and the complication rate (5.9%) declined over the years. If no adenoma was found, exploration of the sella turcica was performed in 45.6%, hypophysectomy in 3.5%, and hemihypophysectomy in 50.9% of these patients, leading to an early remission in 37.9%. In case of persistence or recurrence, further treatment (repeated operation, adrenalectomy, radio-therapy, or medical treatment) was used to control the disease. CONCLUSIONS: Microsurgery remains the treatment of first choice in CD, even though no improvement in remission rates was observed over the years, because complication or remission rates for other treatment options are comparable or worse.


Assuntos
Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/cirurgia , Microcirurgia , Hipersecreção Hipofisária de ACTH/cirurgia , Adenoma Hipofisário Secretor de ACT/complicações , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma/complicações , Adenoma/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Competência Clínica , Estudos de Coortes , Feminino , Humanos , Hipofisectomia , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/etiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
10.
Pathol Res Pract ; 203(4): 221-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17395399

RESUMO

A 44-year-old male suffered from an inactive pituitary adenoma measuring 20mm in computed tomography (CT) scan and nuclear magnetic resonance tomography (NMR). The tumor was surgically resected via the transnasal-transsphenoidal route. Surgical specimens revealed a typical, sparsely granulated adrenocorticotropic hormone (ACTH) cell adenoma, but also a granulomatous inflammation mostly in the periphery of the tumor, corresponding to a granulomatous hypophysitis. This coincidence appears to be unique and has yet not been described in the literature. Therefore, the clinical data and the pathohistologic and ultrastructural findings are presented here.


Assuntos
Adenoma Hipofisário Secretor de ACT/complicações , Adenoma Hipofisário Secretor de ACT/ultraestrutura , Adenoma/complicações , Adenoma/ultraestrutura , Doenças da Hipófise/complicações , Doenças da Hipófise/patologia , Adulto , Isquemia Encefálica/complicações , Granuloma/complicações , Granuloma/patologia , Humanos , Imuno-Histoquímica , Achados Incidentais , Imageamento por Ressonância Magnética , Masculino , Microscopia Eletrônica de Transmissão , Tomografia Computadorizada por Raios X
11.
Acta Neuropathol ; 113(5): 585-90, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17221204

RESUMO

Activation of the Wnt/wingless signalling cascade is a key mechanism in developmental morphogenesis, whereas aberrant nuclear accumulation of beta-catenin in adult tissues seems to be associated with neoplastic transformation and tumour progression. Adamantinomatous craniopharyngiomas carry activating mutations in exon 3 of the beta-catenin gene, which results in a distinct pattern of nuclear beta-catenin accumulation in up to 95% of respective tumour specimens. To better characterise the impact of nuclear beta-catenin aggregation in these neoplasms, we systematically examined epithelial differentiation and cell cycle-associated molecules in accumulating compared to non-accumulating tumour cell clusters using a cohort of 65 adamantinomatous craniopharyngiomas. Monoclonal antibodies directed against cytokeratins 5/6 (CK5/6) were utilised to differentiate squamous from simple epithelium, the latter being identified by immunoreactivity for cytokeratins 8 and 18 (CK8/CK18). Intriguingly, nuclear beta-catenin accumulation in whorl-like tumour cell clusters was always associated with a distinct CK8 and CK18 immunoreactivity, whereas surrounding non-accumulating tumour cells showed exclusively squamous differentiation indicated by CK5/6 expression. In addition, a low proliferation activity combined with an increased expression of p21(WAF1/CIP1), a key control protein of the cell cycle, was observed in beta-catenin accumulating cells. Our data support an impact of nuclear beta-catenin on different cytoarchitectural and epithelial differentiation patterns in adamantinomatous craniopharyngiomas.


Assuntos
Craniofaringioma/metabolismo , Craniofaringioma/patologia , Epitélio/crescimento & desenvolvimento , Morfogênese/fisiologia , beta Catenina/metabolismo , Adolescente , Adulto , Idoso , Diferenciação Celular , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Criança , Pré-Escolar , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Epitélio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Queratina-18/metabolismo , Queratina-8/metabolismo , Masculino , Pessoa de Meia-Idade
12.
Am J Surg Pathol ; 30(12): 1595-603, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17122517

RESUMO

Clinical and histopathologic differentiation of cystic lesions from the sellar region, that is, craniopharyngiomas (CPs) and Rathke cleft cysts (RCCs), is challenging and has paramount importance with respect to variable clinical manifestation and adapted surgical treatment strategies in both entities. Here, we retrospectively evaluated clinico-pathologic findings in 81 patients presenting with a cystic tumor located in the sellar region. All patients underwent transsphenoidal or transcranial resections. Microscopic inspection of surgical specimens identified CP in 51 patients, and RCC in 30 patients. Amongst the panel of immunohistochemical marker proteins used for histopathologic analysis, nuclear accumulation of beta-catenin was detectable only in CP. On the basis of the histopathologic and immunohistochemical analysis, clinical presentation (sex, age, ophthalmologic, and endocrinologic deficits), imaging (tumor location, size, and calcification), as well as a description of cyst contents obtained during operation were retrospectively evaluated. In purely cystic CPs, an isointense signal was more frequent in T1-weighted magnetic resonance images and calcification of the tumor capsule in computed tomography scans. In addition, the size of RCC was smaller and this tumor entity was more often located within the sella. Aberrant (nuclear) immunohistochemical staining for beta-catenin appeared, however, as most reliable factor for the differentiation between purely cystic CPs and RCCs, whereas tumor location, tumor size, and calcification of the tumor capsule were less consistent parameters. The data are compatible with distinct pathogenic pathways associated with these related histopathologic entities.


Assuntos
Núcleo Celular/metabolismo , Cistos do Sistema Nervoso Central/patologia , Craniofaringioma/patologia , Neoplasias Hipofisárias/patologia , beta Catenina/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Núcleo Celular/patologia , Cistos do Sistema Nervoso Central/metabolismo , Cistos do Sistema Nervoso Central/cirurgia , Criança , Pré-Escolar , Craniofaringioma/metabolismo , Craniofaringioma/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/cirurgia , Resultado do Tratamento
13.
Neurosurgery ; 58(6): 1108-18; discussion 1108-18, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16723890

RESUMO

OBJECTIVE: The aim of this study was to evaluate the role of transsphenoidal selective adenomectomy alone or in combination with adjuvant therapy in treatment of recurrent Cushing's disease. METHODS: A total of 16 patients with recurrent Cushing's disease underwent reoperation, 15 via a transsphenoidal approach and one via a combined transsphenoidal/transcranial approach. Selective adenomectomies were performed in 13 patients and hemihypophysectomies were performed in three patients. Endocrinologically, recurrence was diagnosed by an overnight 2-mg dexamethasone suppression test. All patients underwent a 1.5-T magnetic resonance imaging scan, and eight patients underwent inferior petrosal sinus sampling. RESULTS: After selective adenomectomy, six of the 13 patients went into remission. Recurrence always occurred at the localization of the original tumor. In three patients without intraoperative tumor detection, hypophysectomy did not lead to remission. In 10 patients with persistent disease, adjuvant therapy (radiotherapy, adrenalectomy) led to normalization of basal cortisol levels in eight patients and clinical remission in one patient. One patient was lost to follow-up. In 10 patients, no evidence of an adenoma was visible on the preoperative magnetic resonance imaging scan. Inferior petrosal sinus sampling allowed correct prediction of the tumor localization in two of eight patients. CONCLUSION: By performing repeated selective adenomectomy, patients with recurrent Cushing's disease can be cured without the risk of endocrine deficits or major complications. Dynamic endocrine tests are of paramount importance for surgical decision making. Imaging and inferior petrosal sinus sampling are not helpful in locating the recurrent tumor. If normalization can not be achieved, adjuvant therapy is mandatory.


Assuntos
Hipersecreção Hipofisária de ACTH/cirurgia , Adenoma/diagnóstico , Adenoma/cirurgia , Dexametasona , Feminino , Glucocorticoides , Humanos , Hidrocortisona/sangue , Hipofisectomia , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia , Hipersecreção Hipofisária de ACTH/sangue , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Radioterapia Adjuvante , Recidiva , Indução de Remissão , Reoperação
14.
Front Horm Res ; 34: 158-184, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16474220

RESUMO

We evaluate the current role of microsurgery for Cushing's disease (CD) and the efficacy of adjuvant treatment modalities. The standard treatment for primary CD remains transsphenoidal surgery followed by adjuvant therapy in cases with persisting hypercortisolism. Moderately severe cases are treated with radiotherapy, while in the very severe adrenalectomy is performed. In our series of primary CD (March 1997 to September 2004, mean observation period 18.8 months) adenomas were confirmed intraoperatively in 84.0% of the cases. Remission was achieved in 75.0% and recurrence was observed in 4.8% of the patients. Complications occurred in 2.0% of the cases and all resolved without resulting in permanent morbidity. In the literature, the rates of intraoperative confirmation of an adenoma vary between 59.1 and 100%, remission rates between 42 and 100%, and recurrence rates between 3.0 and 63.2% depending on the experience of the surgeon and on the definition of remission. These rates have not improved significantly over the years. In experienced hands selective adenomectomy remains the least damaging and most effective treatment modality since it results in rapid clinical improvement if performed successfully. Therefore, it remains the treatment of choice. Patients not cured by surgery alone benefited from a combination of adjuvant treatment tailored to their specific needs using medications, radiation and/or adrenalectomy. In this fashion, we achieved normalization of cortisol levels in 79% and improvement in another 18% of the patients. We expect these rates to increase further once patients treated with radiotherapy begin to experience its full effect within the next few years.


Assuntos
Hipersecreção Hipofisária de ACTH/cirurgia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/cirurgia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
15.
Acta Neuropathol ; 111(3): 264-71, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16421738

RESUMO

Janus kinase (JAK)/signal transducers and activators of transcription (STAT) cascade are required for cytokines, growth factors, G-proteins and hormones (growth hormone and prolactin). Gatekeepers in this pathway are the suppressor of cytokine signalling (SOCS) family of proteins. Their expression level is epigenetically regulated by DNA methylation. We have investigated the CpG island methylation status of SOCS-1 in a cohort of pituitary adenomas (PA; n=57), craniopharyngiomas (CP; n=30) and normal pituitary tissue (NP; n=11) using methylation sensitive single-strand conformation polymorphism analysis (MS-SSCP) and direct sequencing. SOCS-1 hypermethylation was identified in 51% (29/57) of surgical specimens obtained from PA patients. 83% of these tumours were clinically silent. In contrast, no methylation of SOCS-1 was observed in CPs or NPs. Quantitative real-time PCR and western blot analysis confirmed reduced SOCS-1 expression in the majority of pituitary adenomas. The data is compatible with epigenetic silencing of the SOCS-1 gene and constitutive activation of the JAK-STAT pathway in PA. This appears to contribute particularly to those tumours characterized by a hormone-inactive status.


Assuntos
Adenoma/metabolismo , Inativação Gênica , Neoplasias Hipofisárias/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Adenoma/genética , Adolescente , Adulto , Idoso , Craniofaringioma/genética , Craniofaringioma/metabolismo , Metilação de DNA , DNA de Neoplasias/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Janus Quinases/fisiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/genética , Fatores de Transcrição STAT/fisiologia , Transdução de Sinais/fisiologia , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/genética
16.
Acta Neuropathol ; 109(6): 589-97, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15891929

RESUMO

Dysregulation of the Wnt signalling pathway contributes to developmental abnormalities and carcinogenesis of solid tumours. Here, we examined beta-catenin and adenomatous polyposis coli (APC) by mutational analysis in pituitary adenomas (n=60) and a large series of craniopharyngiomas (n=41). Furthermore, the expression pattern of beta-catenin was immunohistochemically analysed in a cohort of tumours and cysts of the sellar region including pituitary adenomas (n=58), craniopharyngiomas (n=57), arachnoidal cysts (n=8), Rathke's cleft cysts (n=10) and xanthogranulomas (n=6). Whereas APC mutations were not detectable in any tumour entity, beta-catenin mutations were present in 77% of craniopharyngiomas, exclusively of the adamantinomatous subtype. All mutations affected exon 3, which encodes the degradation targeting box of beta-catenin compatible with an accumulation of nuclear beta-catenin protein. In addition, a novel 81-bp deletion of this exonic region was detected in one case. Immunohistochemical analysis confirmed a shift from membrane-bound to nuclear accumulation of beta-catenin in 94% of the adamantinomatous tumours. Aberrant distribution patterns of beta-catenin were never observed in the other tumour entities under study. We conclude that beta-catenin mutations and/or nuclear accumulation serve as diagnostic hallmarks of the adamantinomatous variant, setting it apart from the papillary variant of craniopharyngioma.


Assuntos
Craniofaringioma/genética , Proteínas do Citoesqueleto/genética , Genes APC , Neoplasias Hipofisárias/genética , Sela Túrcica/patologia , Transativadores/genética , Adolescente , Adulto , Idoso , Sequência de Bases , Criança , Pré-Escolar , Craniofaringioma/metabolismo , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Hipofisárias/metabolismo , Polimorfismo Conformacional de Fita Simples , Reação em Cadeia da Polimerase Via Transcriptase Reversa , beta Catenina
17.
Neurosurgery ; 53(1): 72-80; discussion 80-1, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12823875

RESUMO

OBJECTIVE: To investigate the benefit of intraoperative low-field magnetic resonance imaging (MRI) in craniopharyngioma surgery. METHODS: We used a 0.2-T Magnetom Open scanner (Siemens Medical Solutions, Erlangen, Germany) that was located in a radiofrequency-shielded operating theater for intraoperative MRI. The head of the patient was placed in the fringe field of the scanner, so that standard microinstruments could be used. In transsphenoidal surgery, T1-weighted coronal and sagittal images were acquired. In transcranial surgery, a three-dimensional, gradient echo, T1-weighted, fast low-angle shot sequence was measured, thus allowing multiplanar reformatting. RESULTS: A total of 21 surgical procedures in craniopharyngioma patients were investigated. In 10 patients, a bifrontal-translaminar approach was used; in 6 patients, the craniopharyngioma was removed via a transsphenoidal approach; and in 5 patients, intraoperative MRI was used to monitor cyst puncture and aspiration. In the craniotomy group, intraoperative imaging depicted a clear tumor remnant in one patient, which was subsequently removed. In another patient, an area of contrast enhancement was interpreted as artifact; however, postoperative follow-up at 3 months was suspicious for a minor remnant. Two of the eight patients with complete removal developed a recurrence during the follow-up period. In the group of patients who underwent primary transsphenoidal surgery (n = 4), complete removal was estimated by the surgeon in three cases. Intraoperative imaging depicted a remaining tumor in one case, leading to further tumor removal; however, follow-up revealed recurrent cysts. CONCLUSION: Intraoperative low-field MRI allows an ultraearly evaluation of the extent of tumor removal in craniopharyngioma surgery in most cases. Imaging showing an incomplete resection offers the chance for further tumor removal during the same operation. However, intraoperative low-field MRI depicting a complete resection does not exclude craniopharyngioma recurrence.


Assuntos
Craniofaringioma/patologia , Craniofaringioma/cirurgia , Cuidados Intraoperatórios/efeitos adversos , Imageamento por Ressonância Magnética/efeitos adversos , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias , Cirurgia Assistida por Computador , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco
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