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1.
Nature ; 629(8014): 1142-1148, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38588696

RESUMO

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer1,2, who were germline BRCA1 and BRCA2 wild type3. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)4, and secondary end points included event-free survival (EFS) and overall survival (OS)5. pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadjuvante , Ftalazinas , Piperazinas , Neoplasias de Mama Triplo Negativas , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Antraciclinas/uso terapêutico , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Genes BRCA1 , Genes BRCA2 , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Resposta Patológica Completa , Ftalazinas/administração & dosagem , Ftalazinas/uso terapêutico , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Intervalo Livre de Progressão , Estudos Prospectivos , Análise de Sobrevida , Fatores de Tempo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/cirurgia , Adolescente , Adulto Jovem
2.
Histopathology ; 81(4): 511-519, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35879836

RESUMO

BACKGROUND AND AIMS: Chromosome 17 alterations affect the assessment of HER2 gene amplification in breast cancer (BC), but its clinical significance remains unclear. This study aimed to identify the prevalence of centromere enumeration probe 17 (CEP17) alterations, and its correlation with response to neoadjuvant therapy (NAT) in BC patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry-equivocal score. METHODS AND RESULTS: A large BC cohort (n = 6049) with HER2 immunohistochemistry score 2+ and florescent in-situ hybridisation (FISH) results was included to assess the prevalence of CEP17 alterations. Another cohort (n = 885) with available clinicopathological data was used to evaluate the effect of CEP17 in the setting of NAT. HER2-amplified tumours with monosomy 17 (CEP17 copy number < 1.5 per nucleus), normal 17 (CEP17 1.5-< 3.0) and polysomy 17 (CEP17 ≥ 3.0) were observed in 16, 59 and 25%, respectively, compared with 3, 74 and 23%, respectively, in HER2-non-amplified tumours. There was no significant relationship between CEP17 alterations and pathological complete response (pCR) rate in both HER2-amplified and HER2-non-amplified tumours. The independent predictors of pCR were oestrogen (ER) negativity in HER2-amplified tumours [ER negative versus positive; odds ratio (OR) = 11.80; 95% confidence interval (CI) = 1.37-102.00; P = 0.02], and histological grade 3 in HER2 non-amplified tumours (3 versus 1, 2; OR = 5.54; 95% CI = 1.61-19.00; P = 0.007). CONCLUSION: The impacts of CEP17 alterations are not as strong as those of HER2/CEP17 ratio and HER2 copy number. The hormonal receptors status and tumour histological grade are more useful to identify BC patients with a HER2 immunohistochemistry-equivocal score who would benefit from NAT.


Assuntos
Neoplasias da Mama , Aberrações Cromossômicas , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Centrômero , Cromossomos Humanos Par 17/genética , Feminino , Amplificação de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente/métodos , Receptor ErbB-2/análise
3.
Int J Gynecol Cancer ; 30(2): 213-220, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31780570

RESUMO

OBJECTIVE: Two randomized phase III trials demonstrated the efficacy and safety of combining bevacizumab with front-line carboplatin/paclitaxel for advanced ovarian cancer. The OSCAR (NCT01863693) study assessed the impact of front-line bevacizumab-containing therapy on safety and oncologic outcomes in patients with advanced ovarian cancer in the UK. METHODS: Between May 2013 and April 2015, patients with high-risk stage IIIB-IV advanced ovarian cancer received bevacizumab (7.5 or 15 mg/kg every 3 weeks, typically for ≤12 months, per UK clinical practice) combined with front-line chemotherapy, with bevacizumab continued as maintenance therapy. Co-primary endpoints were progression-free survival and safety (NCI-CTCAE v4.0). Patients were evaluated per standard practice/physician's discretion. RESULTS: A total of 299 patients received bevacizumab-containing therapy. The median age was 64 years (range 31-83); 80 patients (27%) were aged ≥70 years. Surgical interventions were primary debulking in 21%, interval debulking in 36%, and none in 43%. Most patients (93%) received bevacizumab 7.5 mg/kg with carboplatin/paclitaxel. Median duration of bevacizumab was 10.5 months(range <0.1-41.4); bevacizumab and chemotherapy were given in combination for a median of three cycles (range 1-10). Median progression-free survival was 15.4 (95% CI 14.5 to 16.9) months. Subgroup analyses according to prior surgery showed median progression-free survival of 20.8, 16.1, and 13.6 months in patients with primary debulking, interval debulking, and no surgery, respectively. Median progression-free survival was 16.1 vs 14.8 months in patients aged <70 versus ≥70 years, respectively. The 1-year overall survival rate was 94%. Grade 3/4 adverse events occurred in 54% of patients, the most common being hypertension (16%) and neutropenia (5%). Thirty-five patients (12%) discontinued bevacizumab for toxicity (most often for proteinuria (2%)). CONCLUSIONS: Median progression-free survival in this study was similar to that in the high-risk subgroup of the ICON7 phase III trial. Median progression-free survival was shortest in patients who did not undergo surgery.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Aging Male ; 20(4): 241-249, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28787255

RESUMO

PURPOSE: To test the psychometric properties of the International Prostate Symptom Score (Hong Kong Chinese version 2) (IPSS) in Chinese male patients with benign prostatic hyperplasia (BPH) under secondary care. METHODS: A prospective longitudinal study was done by interviewing subjects at baseline, at 2 week after baseline for assessing test-retest reliability and at 26 week after baseline for assessing responsiveness. All subjects were interviewed to complete a structured questionnaire including IPSS, Short Form-12 Health Survey version 2 (SF-12v2) and Depression Anxiety Stress Scale (DASS). RESULTS: The IPSS HRQOL score had weak correlations with SF-12v2 summary and DASS domain scores. For reliability analysis, Cronbach's alpha coefficient was 0.90 for the seven symptom-related items. The intraclass correlation coefficients of the IPSS total symptom score and HRQOL score were 0.90 and 0.86, respectively. For sensitivity, statistically significant differences were detected between the subjects with BPH and those without for IPSS total symptom score (effect size = 0.68) but not the IPSS HRQOL score. The areas under ROC curves for the IPSS total symptom and HRQOL scores were 0.67 and 0.60, respectively. CONCLUSIONS: The IPSS was valid, reliable instrument in Chinese patients with BPH. The IPSS total symptom score, but not the HRQOL score, is sensitive in differentiating subgroups.


Assuntos
Inquéritos Epidemiológicos , Hiperplasia Prostática/psicologia , Qualidade de Vida , Idoso , Ansiedade/complicações , Estudos de Casos e Controles , Depressão/complicações , Hong Kong , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/fisiopatologia , Psicometria , Reprodutibilidade dos Testes , Estresse Psicológico/complicações
5.
Chin J Cancer Res ; 29(6): 521-532, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29353974

RESUMO

OBJECTIVE: Primary uterine leiomyosarcomas (ULMS) are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. METHODS: We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network (RCN). Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics (FIGO) stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control (LC) and locoregional control (LRC), overall survival (OS) and disease-free survival (DFS) rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. RESULTS: All patients underwent surgery. Seventy-five patients (68%) received adjuvant radiotherapy (RT), including brachytherapy in 18 (16%). Seventeen patients (15%) received adjuvant chemotherapy. Median follow-up was 58 (range, 6-240) months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. CONCLUSIONS: In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.

6.
Urol Int ; 94(1): 31-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25059529

RESUMO

OBJECTIVE: To review a series of inflammatory myofibroblastic tumours (IMTs) of the urinary bladder in 10 hospitals in Hong Kong. METHODS: A database search in the pathology archives of 10 hospitals in Hong Kong from 1995 to 2013 was performed using the key words 'inflammatory myofibroblastic tumour', 'inflammatory pseudotumour' and 'spindle cell lesion'. Patient characteristics, clinical features, histological features, immunohistochemical staining results and treatment outcomes were reviewed. RESULTS: Nine cases of IMT of the urinary bladder were retrieved. The mean age was 45.4 ± 22.8 years (range 11-78). Eight patients (88.9%) presented with haematuria and 5 patients (55.6%) had anaemia with a mean haemoglobin level of 6.8 ± 1.3 g/dl. Histologically, the majority of patients (77.8%) had a compact spindle cell pattern. Anaplastic lymphoma kinase staining was positive in 75% of cases. During a mean follow-up period of 43.4 months (range 8-94), none of them developed any local recurrence or distant metastasis. CONCLUSIONS: A high index of suspicion of IMT should be maintained for young patients presenting with bleeding bladder tumours and significant anaemia. IMTs of the urinary bladder run a benign disease course, and good prognosis can be achieved after surgical resection.


Assuntos
Granuloma de Células Plasmáticas , Doenças da Bexiga Urinária , Adolescente , Adulto , Idoso , Quinase do Linfoma Anaplásico , Anemia/etiologia , Biomarcadores/análise , Biópsia , Criança , Cistectomia , Cistoscopia , Bases de Dados Factuais , Feminino , Granuloma de Células Plasmáticas/complicações , Granuloma de Células Plasmáticas/metabolismo , Granuloma de Células Plasmáticas/patologia , Granuloma de Células Plasmáticas/cirurgia , Hematúria/etiologia , Hong Kong , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptores Proteína Tirosina Quinases/análise , Fatores de Tempo , Resultado do Tratamento , Doenças da Bexiga Urinária/complicações , Doenças da Bexiga Urinária/metabolismo , Doenças da Bexiga Urinária/patologia , Doenças da Bexiga Urinária/cirurgia , Adulto Jovem
7.
Breast Cancer Res Treat ; 147(2): 295-309, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25141981

RESUMO

Activating transcription factor-2 (ATF-2) has been implicated as a tumour suppressor in breast cancer (BC). c-JUN N-terminal kinase (JNK) and p38 MAPK phosphorylate ATF-2 within the activation domain (AD), which is required for its transcriptional activity. To date, the role of ATF-2 in determining response to endocrine therapy has not been explored. Effects of ATF-2 loss in the oestrogen receptor (ER)-positive luminal BC cell line MCF7 were explored, as well as its role in response to tamoxifen treatment. Genome-wide chromatin binding patterns of ATF-2 when phosphorylated within the AD in MCF-7 cells were determined using ChIP-seq. The expression of ATF-2 and phosphorylated ATF-2 (pATF-2-Thr71) was determined in a series of 1,650 BC patients and correlated with clinico-pathological features and clinical outcome. Loss of ATF-2 diminished the growth-inhibitory effects of tamoxifen, while tamoxifen treatment induced ATF-2 phosphorylation within the AD, to regulate the expression of a set of 227 genes for proximal phospho-ATF-2 binding, involved in cell development, assembly and survival. Low expression of both ATF-2 and pATF-2-Thr71 was significantly associated with aggressive pathological features. Furthermore, pATF-2 was associated with both p-p38 and pJNK1/2 (< 0.0001). While expression of ATF-2 is not associated with outcome, pATF-2 is associated with longer disease-free (p = 0.002) and BC-specific survival in patients exposed to tamoxifen (p = 0.01). Furthermore, multivariate analysis confirmed pATF-2-Thr71 as an independent prognostic factor. ATF-2 is important for modulating the effect of tamoxifen and phosphorylation of ATF-2 within the AD at Thr71 predicts for improved outcome for ER-positive BC receiving tamoxifen.


Assuntos
Fator 2 Ativador da Transcrição/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Tamoxifeno/farmacologia , Fator 2 Ativador da Transcrição/genética , Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Células MCF-7 , Fosforilação , Prognóstico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Clin Cancer Res ; 30(3): 532-541, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37939105

RESUMO

PURPOSE: Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor-positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2- MBC). PATIENTS AND METHODS: Women with HR+ HER2- MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance. Primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints included overall survival (OS), safety/tolerability, pharmacokinetics/pharmacodynamics, and quality of life. Exploratory endpoints included cellular biomarkers. RESULTS: 114 patients received efti and 112 patients received placebo. Median age was 60 years (91.6% visceral disease, 84.1% ET-resistant, 44.2% with previous CDK4/6 inhibitor treatment). Median PFS at 7.3 months was similar for efti and placebo. Median OS was not significantly improved for efti (20.4 vs. 17.5 months; HR, 0.88; P = 0.197) but became significant for predefined exploratory subgroups. EORTC QLQC30-B23 global health status was sustained for efti but deteriorated for placebo. Efti increased absolute lymphocyte, monocyte and secondary target cell (CD4, CD8) counts, plasma IFNγ and CXCL10 levels. CONCLUSIONS: Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. OS was not significantly improved globally (2.9-month difference), but was significantly improved in exploratory biomarker subgroups, warranting further studies to clarify efti's role in patients with ET-resistant HER2- MBC.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Ativação Linfocitária , Paclitaxel , Qualidade de Vida , Receptor ErbB-2/metabolismo
9.
ScientificWorldJournal ; 2013: 506062, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23533351

RESUMO

PURPOSE: Kattan and Stephenson nomograms are based on the outcomes of patients with prostate cancer recruited in the USA, but their applicability to Chinese patients is yet to be validated. We aim at studying the predictive accuracy of these nomograms in the Chinese population. PATIENTS AND METHODS: A total of 408 patients who underwent laparoscopic or open radical resection of prostate from 1995 to 2009 were recruited. The preoperative clinical parameters of these patients were collected, and they were followed up regularly with PSA monitored. Biochemical recurrence was defined as two or more consecutive PSA levels >0.4 ng/mL after radical resection of prostate or secondary cancer treatment. RESULTS: The overall observed 5-year and 10-year biochemical recurrence-free survival rates were 68.3% and 59.8%, which was similar to the predicted values by the Kattan and Stephenson nomograms, respectively. The results of our study achieved a good concordance with both nomograms (Kattan: 5-years, 0.64; Stephenson: 5-years, 0.62, 10-years, 0.71). CONCLUSIONS: The incidence of prostate cancer in Hong Kong is increasing together with the patients' awareness of this disease. Despite the fact that Kattan nomograms were derived from the western population, it has been validated in our study to be useful in Chinese patients as well.


Assuntos
Recidiva Local de Neoplasia/diagnóstico , Nomogramas , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico , Povo Asiático , Intervalo Livre de Doença , Seguimentos , Humanos , Incidência , Calicreínas/análise , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Valor Preditivo dos Testes , Período Pré-Operatório , Antígeno Prostático Específico/análise , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/metabolismo
10.
Am J Mens Health ; 17(6): 15579883231205521, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38093710

RESUMO

This study aimed to investigate the prevalence of lower urinary tract symptoms (LUTS) in older men (N= 3056) with benign prostatic hyperplasia (BPH) and its effects on their sexual function and mental health. Descriptive, correlation, and regression analyses were used to explore the relationships between prostate and lower urinary tract health and psychological well-being. Better prostate and lower urinary tract health positively affected psychological well-being, and sexual function also had a positive influence. LUTS have an adverse impact on sexual function and mental health. Early intervention is crucial for mitigating the negative impact of LUTS on the quality of life in older men. Addressing prostate and lower urinary tract health issues through appropriate interventions may improve psychological well-being. Health care professionals must consider the adverse effects of BPH and LUTS on sexual function and mental health, and implement interventions to enhance the overall quality of life in older men.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Masculino , Humanos , Idoso , Hiperplasia Prostática/complicações , Bem-Estar Psicológico , Qualidade de Vida , Próstata , Sintomas do Trato Urinário Inferior/etiologia
11.
Int J Cancer ; 126(7): 1761-9, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19711345

RESUMO

Accurate predictive markers of chemotherapeutic response in early breast cancer are still lacking. The role of tumour growth fraction as a predictor of response to chemotherapy was assessed in early breast cancer. In this study, immunohistochemical expression of MIB1 was studied in a well-characterised series of early (Stages I and II) node-negative breast carcinoma cases (n = 100) with long-term follow-up that have received adjuvant chemotherapy (cyclophosphamide/methotrexate/5-fluorouracil regimen). In addition, 728 cases who did not receive adjuvant chemotherapy were used as a control group. Increased tumour growth fraction was associated with a better response to adjuvant chemotherapy in terms of longer breast cancer specific survival and disease-free interval [hazard ratio (HR) = 0.354, 95% CI = 0.177-0.688, p = 0.003 and HR = 0.396, 95% CI = 0.205-0.768, p = 0.006, respectively]. In contrast to the control group, patients with high growth fraction tumour (>70%) showed an excellent outcome with infrequently reported events during the period of follow-up. Importantly, patients with a low growth fraction (< or =10%) showed frequent recurrences and shorter survival time with outcome comparable to those of high growth fraction who did not receive chemotherapy. Therefore, tumour growth fraction can be used to assign patients into distinct groups showing differential response to adjuvant chemotherapy. Patients with a high growth fraction appear to be ideal candidates for adjuvant chemotherapy while those with low growth fraction are less likely to benefit and are prone to the potential serious side effects of adjuvant chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Antígeno Ki-67/metabolismo , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Linfonodos/metabolismo , Linfonodos/patologia , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento
12.
Breast Cancer Res Treat ; 112(2): 317-25, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18204897

RESUMO

PURPOSE: To characterize diarrhea events in patients with cancer treated with lapatinib as monotherapy or in combination with capecitabine or taxanes. PATIENTS AND METHODS: Eleven clinical trials (phase I, II, or III) in patients with metastatic cancer were analyzed. Lapatinib was administered at doses ranging from 1,000 to 1,500 mg/day as monotherapy (n = 926) or in combination with capecitabine (n = 198) or taxanes (n = 687). Diarrhea events were characterized based on severity, time to onset, duration, required interventions, and clinical outcomes. RESULTS: In the pooled analysis of nine studies, diarrhea occurred in 55% of lapatinib-treated patients and 24% of patients not receiving lapatinib. All grade diarrhea occurred in 51% of patients treated with lapatinib monotherapy and 65% treated with lapatinib plus capecitabine. In a separate analysis, 48% of patients treated with lapatinib plus a taxane experienced diarrhea. Overall, most diarrhea events were grade 1/2. Grade 3 events occurred in <10% of patients and grade 4 events were rare (

Assuntos
Diarreia/etiologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Ensaios Clínicos como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Receptores ErbB/metabolismo , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Lapatinib , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/antagonistas & inibidores , Resultado do Tratamento
13.
Radiographics ; 28(7): 2023-32, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19001656

RESUMO

Mummies associated with the ancient city of Akhmim in Egypt provide an important portal for radiologic research concerning the ancient Egyptian population. As part of an ongoing investigation, a mummy of Akhmimic derivation owned by the Academy of Natural Sciences in Philadelphia, Pennsylvania, was scanned with a 16-detector row computed tomographic scanner. The resultant images helped confirm that the mummy was that of a female in her late teens. Although the deliberate omission of hieroglyphic texts on the painted coffin rendered the deceased individual anonymous, it is noteworthy that great care had been taken in preparing the corpse for burial. The mummy represents conscientious work by the embalmers, work that is broadly consistent with methods used during the early Ptolemaic period for well-to-do persons. Features of bodily decomposition, including the rotary dissociation of the C1 and C2 vertebral bodies and a missing right patella, point to neglect of the body prior to its recovery and mummification. The fact that the body was well prepared but thinly wrapped and interred in an uninscribed coffin further suggests that the deceased was not of the community that eventually performed the mummification. This evidence is not inconsistent with a scenario involving the body's postmortem immersion in water. Although it cannot be determined with certainty whether the deceased was a drowning victim, it appears that the treatment of the body followed protocols developed in connection with an ancient Egyptian tradition that persons dying in, or retrieved from, the Nile River were embalmed with special care.


Assuntos
Múmias/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Cidades , Egito , Feminino , Humanos
14.
BMC Geriatr ; 8: 25, 2008 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-18837985

RESUMO

BACKGROUND: Different smoking cessation programmes have been developed in the last decade but utilization by the elderly is low. We evaluated a pilot mobile smoking cessation service for the Chinese elderly in Hong Kong and identified predictors of quitting. METHODS: The Mobile Smoking Cessation Programme (MSCP) targeted elderly smokers (aged 60 or above) and provided service in a place that was convenient to the elderly. Trained counsellors provided individual counselling and 4 week's free supply of nicotine replacement therapy (NRT). Follow up was arranged at 1 month by face-to-face and at 3 and 6 months by telephone plus urinary cotinine validation. A structured record sheet was used for data collection. The service was evaluated in terms of process, outcome and cost. RESULTS: 102 governmental and non-governmental social service units and private residential homes for the elderly participated in the MSCP. We held 90 health talks with 3266 elderly (1140 smokers and 2126 non-smokers) attended. Of the 1140 smokers, 365 (32%) received intensive smoking cessation service. By intention-to-treat, the validated 7 day point prevalence quit rate was 20.3% (95% confidence interval: 16.2%-24.8%). Smoking less than 11 cigarettes per day and being adherent to NRT for 4 weeks or more were significant predictors of quitting. The average cost per contact was US$54 (smokers only); per smoker with counselling: US$168; per self-reported quitter: US$594; and per cotinine validated quitter: US$827. CONCLUSION: This mobile smoking cessation programme was acceptable to elderly Chinese smokers, with quit rate comparable to other comprehensive programmes in the West. A mobile clinic is a promising model to reach the elderly and probably other hard to reach smokers.


Assuntos
Promoção da Saúde/organização & administração , Unidades Móveis de Saúde/organização & administração , Cooperação do Paciente/estatística & dados numéricos , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Avaliação Geriátrica , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Projetos Piloto , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Valores de Referência , Medição de Risco , Fatores Sexuais , Fumar/epidemiologia , Fatores de Tempo , Resultado do Tratamento
15.
Surg Pract ; 22(3): 105-110, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30147745

RESUMO

AIM: The intrathecal baclofen pump is an effective treatment for spasticity. However, long-term results have reported patients' dissatisfaction and perception of disability. Potential causes include a frequent need for baclofen pump refill and risks of complications. The aim of the present study was to evaluate the long-term maintenance, complications and clinical outcome of intrathecal baclofen pumps. PATIENTS AND METHODS: We conducted a 16-year retrospective cohort study of patients with spasticity treated with an intrathecal baclofen pump at a university hospital from 2000 to 2016. The primary outcome was the rate of infection per puncture for baclofen pump refill. Secondary outcomes included the incidence of other complications, such as running out of baclofen causing symptomatic withdrawal symptoms, pump mechanical failure, pump battery end of life and the need for pump replacement. The clinical outcome was assessed by the Modified Ashworth Scale (mAS). RESULTS: In total, 340 follow-up episodes with pump refill procedures were recorded. The average interval between each pump refill was 57.3 days (±15.4 days). The average duration of admission for each pump refill was 4 h and 49 min (from 2 h 23 min to 10 h). There were two events with established infection after puncture for the refill, giving rise to an infection rate per puncture of 0.6 percent (2/340).For the long-term clinical outcome, at an average follow-up period of 7.6 years, the postoperative mAS for spasticity was 2.0 ± 0.756, which was significantly better than the preoperative mAS at 3.75 ± 0.462 (P = 0.001). CONCLUSION: Long-term aftercare with baclofen pump refill was safe, with an infection rate of 0.6 per cent per puncture for each refill. Long-term intrathecal baclofen pump was effective in the treatment of spasticity with persistent significant improvement in the spasticity scale.

16.
Chest ; 131(4): 1157-65, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17426223

RESUMO

BACKGROUND: To achieve greater coverage of the elderly smoking population, the provider/client interface could be broadened to include other professional groups who work with the elderly. We evaluated the effectiveness of a 9-h smoking cessation counseling training program for social workers. METHODS: We recruited 177 social workers and used a preintervention/postintervention longitudinal design, analyzed by multilevel, multivariable modeling to adjust for between-subjects covariables and within-subjects correlation in repeated measurements at baseline, 3 months, 6 months, and 12 months after training. RESULTS: Overall, knowledge improved from a mean score of 6.70 +/- 1.03 (+/- SD) at baseline to 7.35 +/- 0.75 at 12 months (range, 0 to 8 correct responses), attitude from 2.84 +/- 0.41 to 3.10 +/- 0.48, and self-perceived competence from 2.49 +/- 0.38 to 2.85 +/- 0.36 (range, 1 to 4, where 4 is best). On multilevel modeling, three of the four "A"s (ask, advice, assist, arrange as per the Agency for Healthcare Research and Quality framework) registered significant gains from baseline to 12 months overall, whereas "advice" did not show any appreciable change. CONCLUSION: These findings demonstrate that our smoking cessation training program achieved sustained effectiveness in the first year after training in enhancing knowledge, positively shifting attitudes, boosting self-perceived competence, and increasing the self-reported frequency of practicing three of the four As in their routine interaction with elderly clients.


Assuntos
Aconselhamento Diretivo/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto/métodos , Abandono do Hábito de Fumar/métodos , Serviço Social/educação , Adulto , Fatores Etários , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Garantia da Qualidade dos Cuidados de Saúde , Inquéritos e Questionários
17.
Hong Kong Med J ; 13(4): 311-3, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17592176

RESUMO

Ten young ketamine abusers presented with lower urinary tract symptoms to two regional hospitals in Hong Kong. Investigations demonstrated contracted bladders and other urinary tract abnormalities. These types of findings have never been reported before in ketamine abusers. The possible aetiology is also discussed.


Assuntos
Ketamina/intoxicação , Transtornos Relacionados ao Uso de Substâncias/complicações , Bexiga Urinaria Neurogênica/induzido quimicamente , Adulto , Feminino , Humanos , Masculino , Bexiga Urinaria Neurogênica/diagnóstico
18.
JCI Insight ; 2(18)2017 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-28931762

RESUMO

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor outcome; overall survival is approximately 35% at two years and some subgroups have a less than 5% two-year survival. Recently, significant improvements have been made in our understanding of AML biology and genetics. These fundamental discoveries are now being translated into new therapies for this disease. This review will discuss recent advances in AML biology and the emerging treatments that are arising from biological studies. Specifically, we will consider new therapies that target molecular mutations in AML and dysregulated pathways such as apoptosis and mitochondrial metabolism. We will also discuss recent advances in immune and cellular therapy for AML.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Pesquisa Translacional Biomédica , Epigênese Genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Terapia de Alvo Molecular , Mutação
19.
Soc Sci Med ; 63(7): 1846-56, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16828214

RESUMO

In a previous study we proposed the notion of general health promotion action (GHPA) defined as "a general intention and actual practices to take action aimed to promote health." GHPA is a subjective measure of health-promoting lifestyle which may reflect practices aimed to promote health and practices which are taken for non-health reasons but which nonetheless have health benefits. The present prospective study aimed to examine whether baseline stage of change for GHPA predicted health-related lifestyle practices at 24-month follow-up in a representative community-based cohort of 3129 Hong Kong Chinese adults. Overall, 37% of the subjects remained in the same stage, 43% had progressed to later stages, and 20% had regressed to earlier stages of change at follow-up. Baseline maintainers were the most likely to report desirable lifestyle practices at follow-up. They were significantly more likely to have exercised in the past month, consumed at least 2 portions of fruit a day, consumed at least 3 portions of vegetable a day, consumed at least 5 portions of fruit or vegetable a day, have had no episodes of binge drinking in the past month, and have had a dental examination at least once a year. The association remained significant after adjusting for age, gender, education, income and baseline level of respective lifestyle practices, with significantly increasing trends from precontemplation to maintenance stage. We conclude that the predictive validity of stage of change for GHPA was supported from these longitudinal findings, and further research on how GHPA can guide health promotion strategies is warranted.


Assuntos
Comportamentos Relacionados com a Saúde , Promoção da Saúde/métodos , Estilo de Vida , Adolescente , Adulto , Distribuição de Qui-Quadrado , China , Dieta , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estatísticas não Paramétricas , Inquéritos e Questionários , Resultado do Tratamento
20.
J Am Dent Assoc ; 152(7): 502-503, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34176564

Assuntos
Movimento , Humanos
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