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1.
J Appl Res Intellect Disabil ; 36(4): 750-757, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36883334

RESUMO

BACKGROUND: The dynamic risk outcome scales (DROS) was developed to assess treatment progress of clients with mild intellectual disability or borderline intellectual functioning using dynamic risk factors. We studied the predictive value of the DROS on various classifications and severity levels of recidivism. METHOD: Data of 250 forensic clients with intellectual disabilities were linked to recidivism data from the Judicial Information Service in the Netherlands. Receiver operating characteristics (ROC) analyses were used to determine the predictive values. RESULTS: The DROS total score could not significantly predict recidivism. A DROS recidivism subscale predicted general, violent and other recidivism. These predictive values were comparable to those of a Dutch tool validated for risk assessment in the general forensic population. CONCLUSIONS: The DROS recidivism subscale predicted various classifications of recidivism better than chance. At present, the DROS appears to have no added value beyond the HKT-30 for the purpose of risk assessment.


Assuntos
Deficiência Intelectual , Deficiências da Aprendizagem , Reincidência , Humanos , Deficiência Intelectual/epidemiologia , Medição de Risco , Fatores de Risco , Psiquiatria Legal
2.
Res Dev Disabil ; 115: 103988, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34090085

RESUMO

BACKGROUND: Trauma and intellectual disability are highly prevalent in the serious mental ill (SMI). Little is known of their impact on general functioning and quality of life. AIM: This study investigated the association of trauma and intellectual disability (ID) with general functioning and quality of life in SMI. METHODS: Patient characteristics and diagnoses were extracted from electronic patient records. We used the Trauma Screening Questionnaire (TSQ), the Screener for Intelligence and Learning Disabilities (SCIL), the Health of the Nation Outcome Scale (HoNOS) and the Manchester Short Assessment of Quality of Life (MANSA) to asses trauma, intellectual impairment, general functioning and quality of life. Proportions on cut-off scores were analysed with cross-tabulations, questionnaire scores with t-tests. Multivariable associations were determined by logistic regression analysis. RESULTS: 611 patients from an outpatient service were assessed. Trauma and ID were associated with each other (r = -0.207). Trauma was associated with worse general functioning and a lower quality of life. Mild intellectual disability (MID) or borderline intellectual functioning (BIF) were associated with worse general functioning. CONCLUSIONS: For patients with SMI, trauma and ID should be identified early in care to treat the lower general functioning and quality of life it caused.


Assuntos
Deficiência Intelectual , Deficiências da Aprendizagem , Humanos , Deficiência Intelectual/epidemiologia , Inteligência , Deficiências da Aprendizagem/epidemiologia , Pacientes Ambulatoriais , Qualidade de Vida
3.
Oncoimmunology ; 10(1): 1935104, 2021 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-34123576

RESUMO

CD103-positive tissue resident memory-like CD8+ T cells (CD8CD103 TRM) are associated with improved prognosis across malignancies, including high-grade serous ovarian cancer (HGSOC). However, whether quantification of CD8, CD103 or both is required to improve existing survival prediction and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration, remains unclear. To address this question, we applied image-based quantification of CD8 and CD103 multiplex immunohistochemistry in the intratumoral and stromal compartments of 268 advanced-stage HGSOC patients from two independent clinical institutions. Infiltration of CD8CD103 immune cell subsets was independent of clinicopathological factors. Our results suggest CD8CD103 TRM quantification as a superior method for prognostication compared to single CD8 or CD103 quantification. A survival benefit of CD8CD103 TRM was observed only in patients treated with primary cytoreductive surgery. Moreover, survival benefit in this group was limited to patients with no macroscopic tumor lesions after surgery. This approach provides novel insights into prognostic stratification of HGSOC patients and may contribute to personalized treatment strategies in the future.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Linfócitos T CD8-Positivos , Feminino , Humanos , Linfócitos do Interstício Tumoral , Prognóstico , Subpopulações de Linfócitos T
4.
Tijdschr Psychiatr ; 62(10): 868-877, 2020.
Artigo em Holandês | MEDLINE | ID: mdl-33184818

RESUMO

BACKGROUND: Little is known about the influence of mild intellectual disability/borderline intellectual functioning (mid/biF) or posttraumatic stress disorder (ptsd) on treatment results in severely mentally ill (smi).
AIM: To investigate whether screeners determining mid/biF or ptsd are associated with less favorable treatment outcome in smi.
METHOD: The screener for intelligence and learning disabilities (scil) was used to screen for mid/biF. The trauma screening questionnaire (tsq) was used to detect ptsd. Outcomes of these screeners were associated with repeated measures on the health of the nation outcome scales (HoNOS) in 628 smi at the Mental Care Centre of Oost Brabant.
RESULTS: In 628 patients one or more HoNOS was acquired. In 352 (56%) patients a scil was acquired, in 334 (53%) patients a tsq. The largest improvement was observed in patients not meeting the criteria for mid/biF and/or ptsd. Less improvement was observed in patients with ptsd and a suspected iq between 70-85, estimated with the scil. No significant change on the HoNOS was observed in patients with an estimated iq below 70.
CONCLUSION: Routine screening for mid/biF and ptsd symptoms is important for early recognition of the disorder, resulting in providing better treatment interventions for patients with mid/biF and ptsd.


Assuntos
Deficiência Intelectual , Deficiências da Aprendizagem , Pessoas Mentalmente Doentes , Transtornos de Estresse Pós-Traumáticos , Humanos , Deficiência Intelectual/diagnóstico , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/terapia , Resultado do Tratamento
5.
Eur Psychiatry ; 63(1): e47, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32381136

RESUMO

BACKGROUND: While polypharmacy is common in long-term residential psychiatric patients, prescription combinations may, from an evidence-based perspective, be irrational. Potentially, many psychiatric patients are treated on the basis of a poor diagnosis. We therefore evaluated the DITSMI model (i.e., Diagnose, Indicate, and Treat Severe Mental Illness), an intervention that involves diagnosis (or re-diagnosis) and appropriate treatment for severely mentally ill long-term residential psychiatric patients. Our main objective was to determine whether DITSMI affected changes over time regarding diagnoses, pharmacological treatment, psychosocial functioning, and bed utilization. METHODS: DITSMI was implemented in a consecutive patient sample of 94 long-term residential psychiatric patients during a longitudinal cohort study without a control group. The cohort was followed for three calendar years. Data were extracted from electronic medical charts. As well as diagnoses, medication use and current mental status, we assessed psychosocial functioning using the Health of the Nations Outcome Scale (HoNOS). Bed utilization was assessed according to length of stay (LOS). Change was analyzed by comparing proportions of these data and testing them with chi-square calculations. We compared the numbers of diagnoses and medication changes, the proportions of HoNOS scores below cut-off, and the proportions of LOS before and after provision of the protocol. RESULTS: Implementation of the DITSMI model was followed by different diagnoses in 49% of patients, different medication in 67%, some improvement in psychosocial functioning, and a 40% decrease in bed utilization. CONCLUSIONS: Our results suggest that DITSMI can be recommended as an appropriate care for all long-term residential psychiatric patients.


Assuntos
Benchmarking/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Transtornos Mentais/tratamento farmacológico , Adulto , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Assistência de Longa Duração/estatística & dados numéricos , Estudos Longitudinais , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde
6.
Tijdschr Psychiatr ; 62(12): 1022-1029, 2020.
Artigo em Holandês | MEDLINE | ID: mdl-33443755

RESUMO

BACKGROUND: Little is known about suicide among individuals with mild intellectual disabilities (mid).
AIM: To explore risk factors for suicide among a small group of clients with mid who committed suicide.
METHOD: Case files of 11 clients with mid were analysed using the Integrated Motivational Volitional model.
RESULTS: Most suicides seem to have taken place impulsively and not on the basis of a predetermined plan. Most clients had comorbid mental health problems, predominantly trauma-related, impulse control and externalizing behavioural problems. The (imminent) loss of contact, such as in the case of transfer from one ward to another ward or to a facility, seems an important risk factor for suicide.
CONCLUSION: Clients with mid residing in a treatment facility may have an increased risk of suicide because of an interaction between client characteristics and treatment context.


Assuntos
Deficiência Intelectual , Suicídio , Humanos , Deficiência Intelectual/epidemiologia , Fatores de Risco
7.
Tijdschr Psychiatr ; 62(12): 1040-1048, 2020.
Artigo em Holandês | MEDLINE | ID: mdl-33443757

RESUMO

BACKGROUND: The Dynamic Risk Outcome Scales (DROS) was developed to assess treatment progress of patients with mild intellectual disability (MID) or borderline intellectual functioning (BIF) and severe behavioral and/or psychiatric problems. Because of the focus on dynamic risk factors, practitioners also see this instrument as a tool for risk assessment.
AIM: To investigate the predictive value of the DROS on different classifications and severities of recidivism.
METHOD: DROS data from the routine outcome monitoring (ROM) of 250 forensic patients with MID-BIF who were discharged between 2007 and end of 2014 were linked to recidivism data from the Judicial Information Service.
RESULTS: The DROS total score predicted general, violence and sexual recidivism better than chance (AUCs > 0.58), although the effect was small. A DROS-recidivism subscale predicted general, violence and other recidivism with a medium to large effect (AUCs > 0.67). The predictive values of the DROS total score and DROS-recidivism subscale were comparable to those of the Historic, Clinical, Future (in Dutch: HKT)-30.
CONCLUSION: The DROS total score and DROS-recidivism subscale predict different classifications of recidivism better than chance. However, for risk assessment the DROS appears to have no added value to the HKT-30.


Assuntos
Deficiência Intelectual , Reincidência , Psiquiatria Legal , Humanos , Deficiência Intelectual/diagnóstico , Medição de Risco , Violência
8.
Mol Imaging Biol ; 22(4): 883-890, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31802362

RESUMO

PURPOSE: Chemokine CXCL12 and its receptor CXCR4 are constitutively overexpressed in human cancers. The CXCL12-CXCR4 signaling axis plays an important role in tumor progression and metastasis, but also in treatment-induced recruitment of CXCR4-expressing cytotoxic immune cells. Here, we aimed to demonstrate the feasibility of N-[11C]methyl-AMD3465 positron emission tomography (PET) to monitor changes in CXCR4 density in tumors after single-fraction local radiotherapy or in combination with immunization. PROCEDURE: TC-1 cells expressing human papillomavirus antigens E6 and E7 were inoculated into the C57BL/6 mice subcutaneously. Two weeks after tumor cell inoculation, mice were irradiated with a single-fraction 14-Gy dose of X-ray. One group of irradiated mice was immunized with an alpha-viral vector vaccine, SFVeE6,7, and another group received daily injections of the CXCR4 antagonist AMD3100 (3 mg/kg -intraperitoneal (i.p.)). Seven days after irradiation, all animals underwent N-[11C]methyl-AMD3465 PET. RESULTS: PET imaging showed N-[11C]methyl-AMD3465 uptake in the tumor of single-fraction irradiated mice was nearly 2.5-fold higher than in sham-irradiated tumors (1.07 ± 0.31 %ID/g vs. 0.42 ± 0.05 % ID/g, p < 0.01). The tumor uptake was further increased by 4-fold (1.73 ± 0.17 % ID/g vs 0.42 ± 0.05 % ID/g, p < 0.01) in mice treated with single-fraction radiotherapy in combination with SFVeE6,7 immunization. Administration of AMD3100 caused a 4.5-fold reduction in the tracer uptake in the tumor of irradiated animals (0.24 ± 0.1 % ID/g, p < 0.001), suggesting that tracer uptake is indeed due to CXCR4-mediated chemotaxis. CONCLUSION: This study demonstrates the feasibility of N-[11C]methyl-AMD3465 PET imaging to monitor treatment-induced changes in the density of CXCR4 receptors in tumors and justifies further evaluation of CXCR4 as a potential imaging biomarker for evaluation of anti-tumor therapies.


Assuntos
Radioisótopos de Carbono/química , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Piridinas/química , Receptores CXCR4/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Linhagem Celular Tumoral , Feminino , Camundongos Endogâmicos C57BL , Neoplasias/metabolismo
9.
J Intellect Disabil Res ; 63(8): 1015-1022, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30991450

RESUMO

BACKGROUND: Assertive community treatment (ACT) and Flexible assertive community treatment (FACT) are organisation models for intensive assertive outreach that were originally developed for individuals with severe mental illness. The models are increasingly applied to people with mild intellectual disability (MID) or borderline intellectual functioning (BIF) and challenging behaviour or mental illness. Research on these types of care for this population is limited. To gain experience in FACT MID/BIF in the Netherlands and to obtain insight in its outcomes, four organisations specialised in the treatment of individuals with MID/BIF and challenging behaviour participated in a 6-year implementation and research project. METHODS: A longitudinal study was set up to investigate outcomes over time. Outcome measures concerned admissions to (mental) health care, social and psychological functioning, (risk of) challenging and criminal behaviour, social participation and client satisfaction. Data were analysed using descriptive statistics and linear mixed models. RESULTS: Over time, clients showed improvement in their social and psychiatric functioning and living circumstances. The number of admissions to (mental) health care diminished as well as the number of contacts with police and justice, the level of social disturbance and the risk factors for challenging and criminal behaviour. Problems related to finances, work and substance abuse remained unchanged. CONCLUSIONS: The results are encouraging and give rise to continued development of and broader research on FACT MID/BIF.


Assuntos
Serviços Comunitários de Saúde Mental/métodos , Deficiência Intelectual/reabilitação , Avaliação de Processos e Resultados em Cuidados de Saúde , Adolescente , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos , Índice de Gravidade de Doença , Adulto Jovem
10.
Int J Gynecol Cancer ; 29(2): 392-397, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30665898

RESUMO

BACKGROUND: Patients with ovarian cancer who are diagnosed with Federation of Gynecology and Obstetrics (FIGO) stage IV disease are a highly heterogeneous group with possible survival differences. The FIGO staging system was therefore updated in 2014. OBJECTIVE: To evaluate the 2014 changes to FIGO stage IV ovarian cancer on overall survival. METHODS: We identified all patients diagnosed with FIGO stage IV disease between January 2008 and December 2015 from the Netherlands Cancer Registry. We analyzed the prognostic effect of FIGO IVa versus IVb. In addition, patients with extra-abdominal lymph node involvement as the only site of distant disease were analyzed separately. Overall survival was analyzed by Kaplan-Meier curves and multivariable Cox regression models. RESULTS: We identified 2436 FIGO IV patients, of whom 35% were diagnosed with FIGO IVa disease. Five-year overall survival of FIGO IVa and IVb patients (including those with no or limited therapy) was 8.9% and 13.0%, respectively (p=0.51). Patients with only extra-abdominal lymph node involvement had a significant better overall survival than all other FIGO IV patients (5-year overall survival 25.9%, hazard ratio 0.77 [95% CI 0.62 to 0.95]). CONCLUSION: Our study shows that the FIGO IV sub-classification into FIGO IVa and IVB does not provide additional prognostic information. Patients with extra-abdominal lymph node metastases as the only site of FIGO IV disease, however, have a better prognosis than all other FIGO IV patients. These results warrant a critical appraisal of the current FIGO IV sub-classification.

11.
PLoS One ; 13(10): e0205741, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30335812

RESUMO

This systematic review examines the relationship between sympathetic and parasympathetic activity on the one hand and job stress and burnout on the other, and is registered at PROSPERO under CRD42016035918. BACKGROUND: Previous research has shown that prolonged job stress may lead to burnout, and that differences in heart rate variability are apparent in people who have heightened job stress. AIMS: In this systematic review, the associations between job stress or burnout and heart rate (variability) or skin conductance are studied. Besides, it was investigated which-if any-guidelines are available for ambulatory assessment and reporting of the results. METHODS: We extracted data from relevant databases following the PRESS checklist and contacted authors for additional resources. Participants included the employed adult population comparing validated job stress and burnout questionnaires examining heart rate and electrodermal activity. Synthesis followed the PRISMA guidelines of reporting systematic reviews. RESULTS: The results showed a positive association between job stress and heart rate, and a negative association between job stress and heart rate variability measures. No definite conclusion could be drawn with regard to burnout and psychophysiological measures. No studies on electrodermal activity could be included based on the inclusion criteria. CONCLUSIONS: High levels of job stress are associated with an increased heart rate, and decreased heart rate variability measures. Recommendations for ambulatory assessment and reporting (STROBE) are discussed in light of the findings.


Assuntos
Esgotamento Profissional/diagnóstico , Sistema Nervoso Parassimpático/fisiologia , Estresse Psicológico/diagnóstico , Sistema Nervoso Simpático/fisiologia , Esgotamento Profissional/fisiopatologia , Resposta Galvânica da Pele/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Satisfação no Emprego , Estresse Psicológico/fisiopatologia , Inquéritos e Questionários
12.
Br J Cancer ; 119(9): 1067-1074, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30356126

RESUMO

BACKGROUND: PORTEC-2 was a randomised trial for women with high-intermediate risk (HIR) endometrial cancer, comparing pelvic external beam radiotherapy (EBRT) with vaginal brachytherapy (VBT). We evaluated long-term outcomes combined with the results of pathology review and molecular analysis. METHODS: 427 women with HIR endometrial cancer were randomised between 2002-2006 to VBT or EBRT. Primary endpoint was vaginal recurrence (VR). Pathology review was done in 97.4%, combined with molecular analysis. RESULTS: Median follow-up was 116 months; 10-year VR was 3.4% versus 2.4% for VBT vs. EBRT (p = 0.55). Ten-year pelvic recurrence (PR) was more frequent in the VBT group (6.3% vs. 0.9%, p = 0.004), mostly combined with distant metastases (DM). Ten-year isolated PR was 2.5% vs. 0.5%, p = 0.10, and DM 10.4 vs. 8.9% (p = 0.45). Overall survival for VBT vs. EBRT was 69.5% vs. 67.6% at 10 years (p = 0.72). L1CAM and p53-mutant expression and substantial lymph-vascular space invasion were risk factors for PR and DM. EBRT reduced PR in cases with these risk factors. CONCLUSION: Long-term results of the PORTEC-2 trial confirm VBT as standard adjuvant treatment for HIR endometrial cancer. Molecular risk assessment has the potential to guide adjuvant therapy. EBRT provided better pelvic control in patients with unfavourable risk factors.


Assuntos
Neoplasias do Endométrio/radioterapia , Pelve/efeitos da radiação , Radioterapia Adjuvante/métodos , Vagina/efeitos da radiação , Idoso , Braquiterapia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Molécula L1 de Adesão de Célula Nervosa/genética , Seleção de Pacientes , Dosagem Radioterapêutica , Análise de Sobrevida , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética
13.
Virchows Arch ; 473(5): 591-598, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30140948

RESUMO

Uterine carcinosarcoma (UCS) has been proposed as a model for epithelial-mesenchymal transition (EMT), a process characterized by a functional change facilitating migration and metastasis in many types of cancer. L1CAM is an adhesion molecule that has been involved in EMT as a marker for mesenchymal phenotype. We examined expression of L1CAM in UCS in a cohort of 90 cases from four different centers. Slides were immunohistochemically stained for L1CAM and scored in four categories (0%, < 10%, 10-50%, and > 50%). A score of more than 10% was considered positive for L1CAM. The median age at presentation was 68.6 years, and half of the patients (53.3%) presented with FIGO stage 1 disease. Membranous L1CAM expression was positive in the epithelial component in 65.4% of cases. Remarkably, expression was negative in the mesenchymal component. In cases where both components were intermingled, expression limited to the epithelial component was confirmed by a double stain for L1CAM and keratin. Expression of L1CAM did not relate to overall or disease-free survival. Our findings suggest L1CAM is either not a marker for the mesenchymal phenotype in EMT, or UCS is not a good model for EMT.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinossarcoma/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Epitélio/metabolismo , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Neoplasias Uterinas/metabolismo , Idoso , Carcinossarcoma/patologia , Epitélio/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Uterinas/patologia
14.
Int J Offender Ther Comp Criminol ; 62(8): 2329-2344, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28569075

RESUMO

The UPPS-P seems to be a promising instrument for measuring different domains of impulsivity in forensic psychiatric patients. Validation studies of the instrument however, have been conducted only in student groups. In this validation study, three groups completed the Dutch UPPS-P: healthy student ( N = 94) and community ( N = 134) samples and a forensic psychiatric sample ( N = 73). The five-factor structure reported previously could only be substantiated in a confirmatory factor analysis over the combined groups but not in the subsamples. Subgroup sample sizes might be too small to allow such complex analyses. Internal consistency, as assessed by Cronbach's alpha, was high on most subscale and sample combinations. In explaining aggression, especially the initial subscale negative urgency (NU) was related to elevated scores on self-reported aggression in the healthy samples (student and community). The current study is the second study that found a relationship between self-reported NU and aggression highlighting the importance of addressing this behavioural domain in aggression management therapy.


Assuntos
Agressão , Comportamento Impulsivo , Inquéritos e Questionários , Adulto , Idoso , Internação Compulsória de Doente Mental , Feminino , Psiquiatria Legal , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Psicometria , Adulto Jovem
15.
Psychiatry Res ; 259: 412-421, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29120851

RESUMO

BACKGROUND: Although several authors have suggested that a single externalizing spectrum encompassing both antisocial behavioral syndromes and substance use disorder is to be preferred, this assumption has not been evaluated systematically throughout studies. PURPOSE: The objective was to establish the generalizability of transdiagnostic models of externalizing disorders across different types of disorders and populations, in regard to the strength of the evidence. METHOD: We conducted a systematic literature review using combinations of two sets of keywords: 1) "antisocial", "externalizing", "conduct disorder", "disruptive behavior disorder", "substance abuse", "substance-related disorder", "cannabis", "cocaine", "hallucinogen", "alcoholism", "opioid"; 2) "latent structure", "factor analysis", "multivariate analysis". RESULTS: Models supporting a superordinate factor appeared dominant in a limited set of different populations, on which the majority of the research sample was focused. CONCLUSIONS: Although the externalizing spectrum model is a promising angle for future research and treatment, extending research on this model in a higher diversity of populations is recommended to enhance the understanding and applicability of the externalizing spectrum model.


Assuntos
Transtorno da Personalidade Antissocial/diagnóstico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/diagnóstico , Transtorno da Conduta/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Humanos , Síndrome
16.
Eur J Cancer ; 86: 285-295, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29059634

RESUMO

BACKGROUND: Human Leucocyte Antigen- E (HLA-E) has been reported as both a positive and negative prognostic marker in cancer. This apparent discrepancy may be due to opposing actions of HLA-E on tumour-infiltrating immune cells. Therefore, we evaluated HLA-E expression and survival in relation to the presence of intratumoural natural killer (NK) cells and cytotoxic T cells (CTLs). METHODS: Tissue microarrays (TMAs) of endometrial tumours were used for immunohistochemical staining of parameters of interest. The combined impact of clinical, pathological and immune parameters on survival was analysed using log rank testing and Cox regression analyses. RESULTS: Upregulation of HLA-E was associated with an improved disease-free and disease-specific survival in univariate analysis (HR 0.58 95% CI 0.37-0.89; HR 0.42 95% CI 0.25-0.73, respectively). In multivariate analysis, the presence of NK cells predicts survival with a hazard ratio (HR) 0.28 (95% confidence interval (CI) 0.09-0.91) when HLA-E expression is upregulated; but it is associated with a worse prognosis when HLA-E expression is normal (HR 13.43, 95% CI 1.70-106.14). By contrast, the prognostic benefit of T cells was not modulated by HLA-E expression. CONCLUSIONS: Taken together, we demonstrate that the prognostic benefit of NK cells, but not T-cells, is influenced by HLA-E expression in endometrial cancer (EC) and propose a model to explain our observations.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias do Endométrio/imunologia , Antígenos de Histocompatibilidade Classe I/análise , Células Matadoras Naturais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Microambiente Tumoral , Progressão da Doença , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Linfócitos T/imunologia , Fatores de Tempo , Análise Serial de Tecidos , Resultado do Tratamento , Regulação para Cima , Antígenos HLA-E
17.
Int J Qual Health Care ; 29(6): 810-816, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29025074

RESUMO

OBJECTIVE: Emphasis on improving healthcare quality has led to centralization of services for patients suspected of ovarian cancer. As centralization of services may induce treatment delays, we aimed to assess compliance with health system interval guidelines in patients suspected of ovarian cancer. DESIGN: Evaluation of health system intervals, comparison between direct and indirect referrals and between 2013 and 2014. SETTING: A managed clinical network (MCN) comprising 11 hospitals in the Netherlands. PARTICIPANTS: Patients that were treated for ovarian cancer within the University Medical Center Groningen in 2013 and 2014. INTERVENTION: Introduction of an MCN to centralize services for patients suspected of ovarian cancer. MAIN OUTCOME MEASURE: Compliance with national guidelines regarding health system intervals. RESULTS: Between 2013 and 2014 a clinically relevant improvement in compliance with guidelines was demonstrated. Within this period, median treatment intervals decreased from 34 to 29 days, and the percentage of patients in which treatment interval guidelines were met increased from 63.5 to 72.2%. New regulations and increased awareness of health system intervals inspired changes in local practice leading to improved compliance with guidelines. Compliance was highest in patients that were directly referred to our academic hospital. CONCLUSION: Evaluation of health system intervals in patients suspected of ovarian cancer was feasible and may be applicable to other MCNs. Though compliance with guidelines improved within the study period, there is potential for improvement. To facilitate real-time evaluation of compliance with national guidelines establishing uniformity of electronic patient files in the MCN is deemed essential.


Assuntos
Serviços Centralizados no Hospital/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Neoplasias Ovarianas/terapia , Tempo para o Tratamento/estatística & dados numéricos , Serviços Centralizados no Hospital/normas , Feminino , Humanos , Programas de Assistência Gerenciada/estatística & dados numéricos , Países Baixos , Garantia da Qualidade dos Cuidados de Saúde
19.
Gynecol Oncol ; 146(2): 327-333, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28511869

RESUMO

BACKGROUND: The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway. METHODS: We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data were used to analyse TP63 mutations and copy-number alterations using cBioPortal. TP53 was silenced in two endometrial cancer cell lines to study its effect on p21 and p63. RESULTS: About half of the tumours showed a p53 mutant phenotype and there was a strong negative correlation with p21 expression. Being marker positive for pp63 or mdm2 was associated with a significantly increased likelihood of dying, [hazard ratios 5.93 (95% CI 2.37-7.27) and 7.48 (95% CI 3.04-9.39), respectively]. These findings were seen in both p53 wildtype and p53 mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63 alteration. Upon silencing of TP53, p21 expression was decreased in one cell line, but no effects on p63 were observed. CONCLUSION: Markers of the p53 pathway improve stratification of endometrial cancers and provide novel insights into the role of this pathway in the disease.


Assuntos
Adenocarcinoma de Células Claras/metabolismo , Carcinoma Endometrioide/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias do Endométrio/metabolismo , Neoplasias Císticas, Mucinosas e Serosas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Linhagem Celular Tumoral , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Inativação Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Invasividade Neoplásica , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/mortalidade , Neoplasias Císticas, Mucinosas e Serosas/patologia , Fosfoproteínas , Prognóstico , Modelos de Riscos Proporcionais , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Adulto Jovem
20.
Gynecol Oncol ; 146(2): 380-385, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28552255

RESUMO

OBJECTIVES: Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years. METHODS: Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed. RESULTS: Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014. CONCLUSION: While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients.


Assuntos
Adenocarcinoma de Células Claras/terapia , Carcinoma Endometrioide/terapia , Quimioterapia Adjuvante/estatística & dados numéricos , Neoplasias do Endométrio/terapia , Fidelidade a Diretrizes/estatística & dados numéricos , Histerectomia , Neoplasias Císticas, Mucinosas e Serosas/terapia , Guias de Prática Clínica como Assunto , Radioterapia Adjuvante/estatística & dados numéricos , Sistema de Registros , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Císticas, Mucinosas e Serosas/patologia , Países Baixos , Melhoria de Qualidade , Risco
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