RESUMO
BACKGROUND: Immunotherapy combined with chemotherapy significantly improves progression-free survival (PFS) compared to first-line chemotherapy alone in advanced endometrial cancer (EC), with a much larger effect size in microsatellite instability-high (MSI-H) cases. New biomarkers might help to select patients who may have benefit among those with a microsatellite-stable (MSS) tumor. PATIENTS AND METHODS: In a pre-planned translational analysis of the MITO END-3 trial, we assessed the significance of genomic abnormalities in patients randomized to standard carboplatin/paclitaxel without or with avelumab. RESULTS: Out of 125 randomized patients, 109 had samples eligible for next-generation sequencing analysis, and 102 had MSI tested. According to The Cancer Genome Atlas (TCGA), there were 29 cases with MSI-H, 26 with MSS TP53 wild type (wt), 47 with MSS TP53 mutated (mut), and 1 case with POLE mutation. Four mutated genes were present in >30% of cases: TP53, PIK3CA, ARID1A, and PTEN. Eleven patients (10%) had a BRCA1/2 mutation (five in MSI-H and six in MSS). High tumor mutational burden (≥10 muts/Mb) was observed in all MSI-H patients, in 4 out of 47 MSS/TP53 mut, and no case in the MSS/TP53 wt category. The effect of avelumab on PFS significantly varied according to TCGA categories, being favorable in MSI-H and worst in MSS/TP53 mut (P interaction = 0.003); a similar non-significant trend was seen in survival analysis. ARID1A and PTEN also showed a statistically significant interaction with treatment effect, which was better in the presence of the mutation (ARID1A P interaction = 0.01; PTEN P interaction = 0.002). CONCLUSION: The MITO END-3 trial results suggest that TP53 mutation is associated with a poor effect of avelumab, while mutations of PTEN and ARID1A are related to a positive effect of the drug in patients with advanced EC.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Endométrio , Instabilidade de Microssatélites , Mutação , Paclitaxel , Humanos , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Idoso , Carboplatina/administração & dosagem , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Imunoterapia/métodos , PTEN Fosfo-Hidrolase/genética , Adulto , Intervalo Livre de Progressão , Biomarcadores Tumorais/genética , Proteína Supressora de Tumor p53/genética , Proteínas de Ligação a DNA/genética , Sequenciamento de Nucleotídeos em Larga Escala , Fatores de Transcrição , Classe I de Fosfatidilinositol 3-QuinasesRESUMO
PURPOSE: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. METHODS: We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). RESULTS: Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9-7.2) and 12.1 months (95% CI: 9.6-16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0-18.4), 6.1 months (95% CI: 4.0-8.9) for CTX-based and 5.3 months (95% CI: 4.1-9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3-16.7 and CTX-based ones (95%CI: 8.7-52.8). Tumour response, PFS and OS decreased proportionally in later lines. CONCLUSION: This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.
Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Receptor ErbB-2/genética , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT's activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75-98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3-4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.
Assuntos
Neoplasias da Mama , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Administração Metronômica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Current guidelines consider vitamin K antagonists (VKA) the oral anticoagulant agents of choice in adults with atrial arrhythmias (AA) and moderate or complex forms of congenital heart disease, significant valvular lesions, or bioprosthetic valves, pending safety data on non-VKA oral anticoagulants (NOACs). Therefore, the international NOTE registry was initiated to assess safety, change in adherence and quality of life (QoL) associated with NOACs in adults with congenital heart disease (ACHD). METHODS: An international multicenter prospective study of NOACs in ACHD was established. Follow-up occurred at 6â¯months and yearly thereafter. Primary endpoints were thromboembolism and major bleeding. Secondary endpoints included minor bleeding, change in therapy adherence (≥80% medication refill rate, ≥6 out of 8 on Morisky-8 questionnaire) and QoL (SF-36 questionnaire). RESULTS: In total, 530 ACHD patients (mean age 47 SD 15â¯years; 55% male) with predominantly moderate or complex defects (85%), significant valvular lesions (46%) and/or bioprosthetic valves (11%) using NOACs (rivaroxaban 43%; apixaban 39%; dabigatran 12%; edoxaban 7%) were enrolled. The most common indication was AA (91%). Over a median follow-up of 1.0 [IQR 0.0-2.0] year, thromboembolic event rate was 1.0% [95%CI 0.4-2.0] (nâ¯=â¯6) per year, with 1.1% [95%CI 0.5-2.2] (nâ¯=â¯7) annualized rate of major bleeding and 6.3% [95%CI 4.5-8.5] (nâ¯=â¯37) annualized rate of minor bleeding. Adherence was sufficient during 2â¯years follow-up in 80-93% of patients. At 1-year follow-up, among the subset of previous VKA-users who completed the survey (nâ¯=â¯33), QoL improved in 6 out of 8 domains (pâ¯âªâ¯0.05). CONCLUSIONS: Initial results from our worldwide prospective study suggest that NOACs are safe and may be effective for thromboembolic prevention in adults with heterogeneous forms of congenital heart disease.
Assuntos
Bioprótese/estatística & dados numéricos , Inibidores do Fator Xa , Cardiopatias Congênitas , Doenças das Valvas Cardíacas , Hemorragia , Implantação de Prótese/efeitos adversos , Qualidade de Vida , Tromboembolia , Adolescente , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/classificação , Feminino , Saúde Global/estatística & dados numéricos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/tratamento farmacológico , Cardiopatias Congênitas/psicologia , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/epidemiologia , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Implantação de Prótese/instrumentação , Sistema de Registros/estatística & dados numéricos , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controleRESUMO
Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3-10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8-11.3, HRâ¯=â¯0.72) and in CAPE-single agent (10.7, 95%CI 8.3-15.8, HRâ¯=â¯0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.
Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Aim of the study was to propose a method to define the relationship of not allergic contact dermatitis with chemical risk factors in workplace. This method evaluates the skin response to simultaneous chemical and mechanical stimulation, made with a soft bristle brush. The method has been used on 9 cases of not allergic skin diseases, observed from 2000 to 2006 in Occupational Medicine Division of "Federico II" University of Naples. The greatest part of pathologies had the polymorphous pattern of skin inflammation, characterized by subintrant erythema, suspected of occupational origin. In 6 cases a stronger reaction to both chemical and mechanical stimulation was highlighted, confirming a possible occupational etiology. In 1 case the occupational origin was excluded, while in 2 cases the skin response was uncertain. The method does not define all cases of occupational skin pathologies, but it seems to be very useful to diagnostic and insurance needs.
Assuntos
Dermatite Ocupacional/diagnóstico , Dermatite Ocupacional/etiologia , Feminino , Humanos , MasculinoRESUMO
Late arterial hypertension has been identified as a major predictor for morbidity and mortality in aortic coarctation (AoC) patients. Few data are available about efficacy and tolerability of angiotensin converting enzyme inhibitors vs beta-blockers in young AoC patients. This study aimed to evaluate the tolerability and efficacy on 24-h blood pressure (BP) and left ventricular mass/height(2.7) (LVMI), of atenolol vs enalapril. We enrolled consecutive AoC hypertensive patients with (a) no history of BP treatment or after >48 h of withdrawn, (b) aged 6-20 years, (c) body mass index (BMI) <90th percentile for age and sex, (d) >12 months from a successful AoC repair and (e) no major associated cardiovascular abnormalities. All patient were evaluated with 24-h ambulatory BP monitoring, standard echocardiography, strain-strain rate imaging, at enrolment, 3, 6 and 12 months of treatment. We studied 51 AoC patients (13±3.9 years, BMI: 21.4±4.3 kg m(-2)). Patients were randomly assigned at atenolol treatment (n=26), or enalapril treatment (n=25). The mean follow-up duration was 11±2 months. Both drugs were able to significantly reduce 24-systolic BP (SBP; atenolol: 133±11 mm Hg vs 124±16 mm Hg, P=0.016; enalapril: 135±6 mm Hg vs 127±7 mm Hg, P=0.001). Only enalapril was able to significantly reduce LVMI (47±12 vs 39.6±10 g m(-)(2.7), P=0.016). Only in atenolol group in two cases (7.7%) drug withdrawal was needed because of adverse events. Enalapril and atenolol are similarly effective in reducing SBP. However, only enalapril demonstrated a significant reduction of LVMI. In no case, enalapril was stopped because of adverse events.
Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Coartação Aórtica/cirurgia , Atenolol/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Procedimentos Cirúrgicos Cardíacos , Enalapril/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Coartação Aórtica/complicações , Coartação Aórtica/diagnóstico , Coartação Aórtica/fisiopatologia , Atenolol/efeitos adversos , Criança , Enalapril/efeitos adversos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipertensão/fisiopatologia , Itália , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The aim of the present study was to evaluate the influence of changes in the serum calcium concentration upon glucagon secretion in man. For this purpose, a group of subjects with either idiopathic (four cases) or secondary (two cases) hypoparathyroidism was submitted to an arginine test (0.5 g/kg) before and after the correction of hypocalcemia. In the presence of hypocalcemia, the glucagon response to the amino acid was modest and delayed (glucagon peak, 150 +/- 28 pg/ml). The acute correction of hypocalcemia produced a striking increase in basal glucagon levels (125 +/- 24 vs. 75 +/- 15 pg/ml; P less than 0.01) and restored the glucagon peak in response to arginine (270 +/- 50 pg/ml; P less than 0.01). The increase in plasma glucose triggered by arginine was augmented under normocalcemic conditions, while the pattern of plasma insulin response was quite similar. These results indicate that glucagon secretion in man is critically dependent on the serum calcium concentration.
Assuntos
Cálcio/uso terapêutico , Glucagon/metabolismo , Hipocalcemia/sangue , Hipoparatireoidismo/sangue , Adulto , Arginina , Glicemia/metabolismo , Feminino , Humanos , Hipocalcemia/tratamento farmacológico , Hipocalcemia/etiologia , Hipoparatireoidismo/complicações , Insulina/sangue , Cinética , Masculino , Pessoa de Meia-IdadeRESUMO
In this study we evaluated the influence of changes in serum calcium concentration upon somatostatin-mediated inhibition of insulin secretion in man. For this purpose, we investigated the effect of somatostatin in a group of subjects with hypoparathyroidism before and after correction of hypocalcemia and in normal subjects made hypercalcemic by exogenous calcium administration. In the presence of hypocalcemia, somatostatin caused an almost total inhibition of glucose-induced insulin secretion. In addition, somatostatin significantly decreased glucose tolerance in those hypocalcemic patients who exhibited normal tolerance under basal conditions [glucose utilization (kG), 1.44 +/- 0.13 before vs. 0.68 +/- 0.14 during somatostatin; P < 0.02]. Glucose tolerance was unaltered in those subjects who had a decreased glucose tolerance under basal conditions (kG, 1.01 +/- 0.1 before vs. 0.88 +/- 0.16 during somatostatin; P = NS). Under normocalcemic conditions, the insulin response to glucose and glucose tolerance were significantly greater than values measured during hypocalcemia. However, somatostatin blunted the insulin response to glucose and significantly decreased glucose utilization. These inhibitory effects of somatostatin upon insulin secretion and glucose tolerance were not reversed by a concurrent infusion of calcium (serum calcium, 6.9 +/- 0.3 meq/liter) in a group of normal subjects. Our data confirm the reduced insulin secretion and glucose tolerance in hypoparathyroidism and demonstrate that the suppressive effect of somatostatin upon glucose-stimulated insulin secretion is independent of changes in serum calcium concentration over a wide range.
Assuntos
Cálcio/sangue , Hipoparatireoidismo/metabolismo , Insulina/metabolismo , Somatostatina/fisiologia , Adulto , Feminino , Glucose , Teste de Tolerância a Glucose , Humanos , Hipercalcemia/metabolismo , Hipocalcemia/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
The occurrence of an angiosarcoma of the residual breast after conservative surgery and adjuvant radiotherapy for early mammary carcinoma is a very rare event. In western countries only 57 cases have been published in the literature (5 in Italy) since the first described case in 1987. Radiotherapy seems to be the most important etiological factor in the development of the neoplasm. Diagnosis is often delayed, owing to the "benign" aspect of the lesion. The only effective treatment is residual mastectomy, because chemotherapy is ineffective. The prognosis is often dismal, because of the aggressive behaviour of the lesion in most cases. The case of a patient with a multicentric secondary angiosarcoma of the breast recently operated on is described.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Hemangiossarcoma/patologia , Neoplasias Induzidas por Radiação/patologia , Idoso , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Feminino , Hemangiossarcoma/cirurgia , Humanos , Mastectomia Segmentar , Neoplasias Induzidas por Radiação/cirurgia , Radioterapia AdjuvanteRESUMO
Assessment of presence of metastatic disease (m.d.) in bladder cancer (b.c.) can represent a main problem as influencing the appropriate therapeutic policy (mostly the indication to radical surgery). Evaluation of the real cost-effectiveness ratio of radiographic and radionuclide diagnostic work-up induced us to retrospectively review historical data about our b.c. patients (pts). From March 1988 to June 1991, 76 not consecutive pts with histologically proven bladder cancer were included in this study. 5 Pts were staged as T1, 25 as T2, 18 as T3a, 23 as T3b, 5 as T4. 2 Pts were graded as G1, 27 as G2, 44 as G3, 3 as Gx. Age varied from 39 to 89 years (average: 62.3). 79 Pts underwent the "basic work-up" (including chest plain film, bone and liver scans) and at least one follow-up control. 266 chest plain films, 22 chest x-ray tomograms, 2 chest CT scans, 27 bone x-ray tomograms, 231 bone scans, 240 liver scans, 17 liver ultrasonographies were totally realized. All pts underwent at least an abdomen-pelvic CT, but related results are not considered in the study. Fine needle aspiration cytologic biopsies were realized in selected cases; also these results are not selectively reported here. Together with cytologic positive results, only progression of m.d. was considered as its definite presence. Conventional x-ray examination (plain film integrated by x-ray tomograms of "suspicious" findings) resulted sufficiently complete and accurate to reveal chest m.d. Concerning skeletal diagnostic survey, only 6 pts (26%) out of 23 pts with "positive" bone scans really resulted affected by m.d.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Metástase Neoplásica/diagnóstico , Neoplasias da Bexiga Urinária , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Metástase Linfática , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico por imagem , Cintilografia , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/secundário , Neoplasias Torácicas/diagnóstico por imagem , Neoplasias Torácicas/secundário , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
The epithelial-mesenchymal transition (EMT) is a program involved in embryonic development that is often activated during cancer invasion and metastasis. CD133 is the main marker identifying cancer stem cells (CSCs) in lung cancer. Circulating tumor cells (CTCs) are demonstrated to be useful as a biomarker for the diagnosis and treatment of cancer. The aim of this study was to correlate EMT, CSCs and CTCs with patient prognosis to verify whether they can contribute to better stratification of lung cancer patients at risk for recurrent and metastatic disease. Pulmonary venous blood was drawn after major pulmonary surgery in 45 patients with resectable non-small cell lung cancer (NSCLC) in order to identify CTCs. For the same patients, we also constructed prognostic lung tissue microarrays (TMA) for CD133 and c-kit and evaluated CSC and EMT markers using flow cytometry. Cytokeratin-positive cells were detectable in 11 (23.9%) cases. c-kit expression was heterogeneous in prognostic TMAs while CD133 expression was low or absent which was also confirmed by flow cytometry and RT-PCR. Flow cytometric analysis showed that the mean percentage of cells with CD133 expression was 1.6%. CD90 and CD326 markers were co-expressed with a mean percentage of 10.41%. When CD133 and CD90/CD326 expression was correlated with follow-up, CD133 showed a higher correlation with deceased patients when compared with CD90/CD326 co-expression (32.5 vs. 9.5%). CD133 expression demonstrated a strong significant association with patients exhibiting progressive disease when compared to CD90/CD326 expression (15 vs. 7.1%). CD133 may be significantly associated with invasion and metastatic spread of NSCLC. The co-expression of CD90, CD326 and CD133 has definite prognostic value in patients with NSCLC.
Assuntos
Neoplasias Pulmonares/patologia , Células Neoplásicas Circulantes/patologia , Células-Tronco Neoplásicas/patologia , Antígenos CD/genética , Antígenos CD/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Transição Epitelial-Mesenquimal , Feminino , Humanos , Queratinas/genética , Queratinas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Veias Pulmonares/metabolismoRESUMO
Urinary bladder cancer is a common malignancy in industrialized countries. More than 90% of bladder cancer originates in the transitional cells. Bladder transitional cancer prognosis is, according to the most recent definition related to the level of tumor infiltration, characterized by two main phenotypes, Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC). The genetic profile and the clinical course of the two subtypes are completely different, however among NMIBC the prognosis is not completely predictable, since 20% of the cases experience a relapse, even in the form of MIBC. It has recently been reported that the chromosomal region 12q13-15, containing crucial cancer genes such as MDM2, CDK4, GLI and an entire cluster of HOX genes, is amplified in bladder cancer. HOX genes codify for transcriptionl factor, involved in embryonal development and cancer progression, with main nuclear expression. Particularly it was also described the strong involvement of HOX B13 in several tumors of urogenital system. In this study we have been investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX B13 expression in bladder cancer evolution and progression, evaluating its ability to discriminate between NMIBC and MBCI phenotypes. Cytoplasmic HOX B13 delocalization significantly relates with muscle invasion (p 0.004). In addition in the series of NMIBC nuclear HOX B13 expression loss is significantly associated to shorter disease free survival (p-value=0.038) defining a potential prognostic role. Overexpression of HOX B13 in more aggressive phenotype is also demonstrate at gene level by quantitative RT-PCR. The de-regulation and delocalization of HOX B13 in urinary bladder cancer supports again the important role of HOX genes in tumor evolution and represents a starting point to establish an integrated analysis, in which HOX genes represent important prognostic and predictive markers for bladder cancer.
Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
Life expectancy is still reduced in aortic coarctation (AoC) patients despite a successful repair because of late arterial hypertension and atherosclerosis. Masked hypertension (MH) consists of an elevated daytime or awake ambulatory blood pressure (BP) in the presence of a normal BP on conventional measurement at the office. To assess the prevalence of MH among AoC normotensive young patients successfully treated and to evaluate the impact of MH on left ventricular (LV) geometry and function.We studied 76 AoC patients (mean age 14.5±5.7 years, male 64%). According to 24 h ambulatory BP monitoring (ABPM) our sample was divided in real normotensive patients (Group RN, n=40) and MH patients (Group MH, n=36). There was an increased pressure gradient in the aortic arch (15 mm Hg±4 vs 13 mm Hg±4.7, P<0.05), increased LV mass (51 g m(-2.7)±13 vs 46 g m(-2.7)±12, P<0.05), in MH AoC patients. Regional longitudinal deformation properties of the basal septal segment (-15%±2.4 vs -20%±5, P<0.01) and LV twist values (14°±1.6 vs 12°±1.9, P<0.0001) were reduced in the MH group. There is a high prevalence of MH in young patients with repaired AoC, which is associated with abnormal LV structure and function. Clinicians should consider 24 h ABPM measurements in apparently normotensive patients followed up for AoC repair.
Assuntos
Coartação Aórtica/cirurgia , Procedimentos Cirúrgicos Cardiovasculares , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hipertensão Mascarada/complicações , Hipertensão Mascarada/epidemiologia , Adolescente , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Criança , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Hipertensão Mascarada/fisiopatologia , Prevalência , Análise de Regressão , Estudos Retrospectivos , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto JovemRESUMO
A total of 416 gloves were tested for punctures after 200 episiotomy repairs. Evidence of perforation was found in 34 (8%) of the gloves used and in only half the cases did the surgeon actually realise that a perforation had occurred. The left index finger and thumb were more often perforated than other parts of the gloves. The implications of the findings, especially as regards spread of infections to surgeons, are discussed.
Assuntos
Episiotomia , Luvas Cirúrgicas , Feminino , HumanosRESUMO
A survey of glove perforation in 200 consecutive Caesarean sections (100 elective and 100 emergency) was undertaken. A total of 1276 gloves were tested for punctures after the end of the operation. Evidence of perforation of one or more gloves was found following 39 elective (234 gloves, 37.2%) and 43 emergency sections (290 gloves, 44.8%) (total 82, 41%). Only in 17 of these cases (20.7%) was it realised that a perforation had actually occurred. The surgeons were found to be significantly more at risk of perforation than the other members of the operating team.
Assuntos
Cesárea , Emergências , Luvas Cirúrgicas , Ferimentos Penetrantes Produzidos por Agulha/etiologia , Cesárea/instrumentação , Feminino , Humanos , Recém-Nascido , Gravidez , Fatores de Risco , Técnicas de Sutura/instrumentaçãoRESUMO
1. The Mediterranean sponge Reniera sarai, Pulitzeri-Finali, 1969 (Demospongiae: Haploscleridae: Renieridae) possesses in large amounts a series of unprecedented polycyclic alkaloids, saraines 1-3 and saraines A-C. 2. The structural peculiarities of saraines, their chemical-physical characteristics, along with their relevant abundance in the sponge, prompted a study aimed at investigating their biological properties. 3. Saraines were assayed for their cytotoxic, antibacterial, insecticidal and potential antitumoral activities. These results, along with the growth inhibition of fertilized sea urchin eggs, are reported.
Assuntos
Alcaloides/farmacologia , Poríferos/química , Aedes , Agrobacterium tumefaciens , Animais , Artemia/efeitos dos fármacos , Artrópodes , Inseticidas , Ácaros , Tumores de Planta , Ouriços-do-Mar , Staphylococcus aureus/efeitos dos fármacos , Zigoto/efeitos dos fármacos , Zigoto/crescimento & desenvolvimentoRESUMO
We made a study on patients suffering from neoplasias treated with cisplatinum to compare antiemetic efficacy of alizapride or associated to dexamethasone. We divided patients in two groups. We somministred alizapride alone to the first group and alizapride plus dexamethasone to the second one. We evaluated presence or absence of emesis, its intensity and eventual tossic effects due to the drugs through an autocompilative questionnaire given to the patients. Our results didn't show important statistical differences between the two groups, though association with dexamethasone gets better emesis control. Alizapride anyway, didn't present important collateral effects, particularly extrapyramidal ones.
Assuntos
Antieméticos/uso terapêutico , Dexametasona/uso terapêutico , Pirrolidinas/uso terapêutico , Vômito Precoce/tratamento farmacológico , Antieméticos/efeitos adversos , Dexametasona/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pirrolidinas/efeitos adversos , Distribuição Aleatória , Inquéritos e QuestionáriosRESUMO
During the years 1991-1994, 97 anovulatory infertile women with polycystic ovarian syndrome (PCOS) were treated with laparoscopic electrocautery of the ovarian surface after they had failed to ovulate under ovarian stimulation. To assess the endocrinological and clinical outcome and in an attempt to determine the mechanism of action, the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione, testosterone and dehydroepiandrosterone sulfate (DHEAS) were determined before and after laparoscopic ovarian cautery. Fifty regularly cycling women undergoing laparoscopy for investigation of infertility or tubal ligation served as controls. In patients with PCOS but not in controls, the reduction of androgen levels and normalization of cycle length were highly significant. In contrast, LH and FSH levels rose during the first 2 days after the operation. These results resemble those reported after ovarian wedge resection. Ovulation was obtained in 90% (81 of 90) and pregnancy in 81.1% (73 of 90) of the patients; that increased to 84.4%, including the non-responders (nine patients) treated with clomiphene citrate (CC), after electrocautery. The response to ovarian electrocautery was influenced by body weight, with an ovulation rate of 95-96% in the slim and moderately obese women, decreasing to 81-82% in the really obese ones. When ovulation was established, the pregnancy rate was independent of body weight. However, a striking relationship was detected between smoking habits and pregnancy rate subsequent to ovarian electrocautery, ranging from 24% in smokers to 92% in non-smoking couples. In 30 second-look operations, de novo adhesions were found in 23.3% of the patients (7 of 30). Therefore, ovarian electrocautery is an effective procedure to improve the intraovarian mechanism of selecting a dominant follicle for patients with PCOS in whom initial medical management fails, and it appears to be one of the possible treatments for this disease. A possible postoperative complication may be adhesion formation that seem to be lower than after ovarian wedge resection.
Assuntos
Androstenóis/sangue , Eletrocoagulação/métodos , Infertilidade Feminina/cirurgia , Laparoscopia , Ovário/cirurgia , Síndrome do Ovário Policístico/cirurgia , Adulto , Androstenodiona/sangue , Androstenodiona/metabolismo , Androstenóis/metabolismo , Peso Corporal , Estudos de Coortes , Desidroepiandrosterona/sangue , Desidroepiandrosterona/metabolismo , Eletrocoagulação/efeitos adversos , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/metabolismo , Humanos , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Concentração Osmolar , Ovulação/fisiologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/fisiopatologia , Complicações Pós-Operatórias , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Reoperação , Testosterona/sangue , Testosterona/metabolismo , Fatores de Tempo , Aderências Teciduais/etiologia , Resultado do TratamentoRESUMO
The authors have examined endocrine function in women during postmenopausal age. They have also studied polymicrobic vaginal flora related to sexual hormone levels. Have been controllated correlations between vaginal microbic status and cytohormonal response at different hormonal situation present in the same woman. In postmenopausal women have been formed low oestrogen levels related to low presence of Doderlein. Perhaps in postmenopausal women other factors than oestrogen and progesterone levels, could influence vaginal polymicrobic flora.