Place de la laparoscopie dans le traitement du cancer de l'endomètre [Laparoscopy in the management of endometrial cancer]

Les récents progrès de la laparoscopie ont modifié l'approche chirurgicale des patientes atteintes d'un cancer de l'endomètre. Le centre Swissendos Fribourg en collaboration avec l'AGO (Groupe de travail pour la gynécologie oncologique) et l'AGE (Groupe de travail pour la gynécologie endoscopique) ont entrepris d'élaborer un consensus basé sur l'évidence pour la pratique de la laparoscopie dans le traitement du cancer de l'endomètre. L'objectif a été de définir une approche propre à la Suisse en fournissant aux praticiens une aide à la prise en charge. Recent advance in laparoscopy have changed the surgical approach of endometrial cancer patients. The Swissendos Center, Fribourg, in collaboration with AGO (Groupe de travail pour la gynécologie oncologique) and AGE (groupe de travail pour la gynécologie endoscopique) have established a consensus based on the available evidence for the use of laparoscopy in the management of patients with endometrial cancer The main objective was to define Swiss clinical practice guidelines appropriate to the country and consistent with the needs of the physicians.

Cigarette smoking and endometrial cancer risk: the modifying effect of obesity.

The objective of this study was to evaluate the association between cigarette smoking and endometrial cancer risk by investigating potential modifying effects of menopausal status, obesity, and exogenous hormones. We pooled data from three case-control studies with the same study design conducted in Italy and Switzerland between 1982 and 2006. Overall, 1446 incident endometrial cancers and 4076 hospital controls were enrolled. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models, conditioned on study and centre, and adjusted for age, period of interview, age at menarche, parity, and body mass index. In comparison with never smokers, current smokers showed reduced endometrial cancer risk (OR: 0.80; 95% CI: 0.66-0.96), with a 28% decrease in risk for smoking >/=20 cigarettes/day. The association did not vary according to menopausal status, oral contraceptive use, or hormone replacement therapy. However, heterogeneity emerged according to body mass index among postmenopausal women, with obese women showing the greatest risk reduction for current smoking (OR: 0.47; 95% CI: 0.27-0.81). In postmenopausal women, obesity turned out to be an important modifier of the association between cigarette smoking and the risk of endometrial cancer. This finding calls for caution in interpreting the favorable effects of cigarette smoking, considering the toxic and carcinogenic effects of tobacco.

Evidence for different expression profiles for c-Met, EGFR, PTEN and the mTOR pathway in low and high grade endometrial carcinomas in a cohort of consecutive women. Occurrence of PIK3CA and K-Ras mutations and microsatellite instability.

Molecular and genetic investigations in endometrial carcinogenesis may have prognostic and therapeutic implications. We studied the expression of EGFR, c-Met, PTEN and the mTOR signalling pathway (phospho-AKT/phospho-mTOR/phospho-RPS6) in 69 consecutive tumours and 16 tissue microarrays. We also analysed PIK3CA, K-Ras mutations and microsatellite instability (MSI). We distinguished two groups: group 1 (grade 1 and 2 endometrioid cancers) and group 2 (grade 3 endometrioid and type II clear and serous cell cancers). We hypothesised that these histological groups might have different features. We found that a) survival was higher in group 1 with less aggressive tumours (P⟨0.03); b) EGFR (P=0.01), PTEN and the AKT/mTOR/RPS6 signalling pathway were increased in group 1 versus group 2 (P=0.05 for phospho-mTOR); c) conversely, c-Met was higher (P⟨0.03) in group 2 than in group 1; d) In group 1, EGFR was correlated with c-Met, phospho-mTOR, phospho-RPS6 and the global activity of the phospho-AKT/phospho-mTOR/phospho-RPS6 pathway. In group 2, EGFR was correlated only with the phospho-AKT/phospho-mTOR/phospho-RPS6 pathway, whereas c-Met was correlated with PTEN; e) survival was higher for tumours with more than 50% PTEN-positive cells; f) K-RAS and PIK3CA mutations occurred in 10-12% of the available tumours and MSI in 40.4%, with a loss of MLH1 and PMS2 expression. Our results for endometrial cancers provide the first evidence for a difference in status between groups 1 and 2. The patients may benefit from different targeted treatments, anti-EGFR agents and rapamycin derivatives (anti-mTOR) for group 1 and an anti c-MET/ligand complex for group 2.

Cigarette smoking and the risk of endometrial cancer.

The risk of endometrial cancer in relation to cigarette consumption was evaluated in a hospital-based case-control study of breast and genital neoplasms conducted in Milan, northern Italy. For the present analysis, 357 women (cases) with histologically confirmed endometrial cancer were compared to a group of 1122 women (controls) admitted for a large spectrum of acute conditions unrelated to smoking or to any of the known or potential risk factors for endometrial cancer. Compared with never-smokers, the multivariate relative risk estimates were for current 0.45 [95% confidence interval (CI) = 0.30-0.70] and 0.86 (95% CI = 0.50-1.46) for ex-smokers. The negative association of endometrial cancer with current smoking was not influenced by menopausal status as well as by other major identified potential confounding factors, i.e. menstrual and reproductive history, body mass index, oral contraceptive or estrogen replacement therapy use and family gynecologic cancer history. However, there was no evidence of a dose-risk effect, since the relative risks were similar in moderate and heavy smokers. The present study confirms that smoking is less frequent in cases hospitalized for endometrial cancer than in a comparison group of patients with non-smoking-related acute conditions. This negative association is perhaps explained in terms of reduced estrogen levels in smokers, though the influence and the importance of some uncontrolled selection bias (due, for instance, to longer hospital stay of smokers even when admission diagnosis was for non-smoking-related conditions) cannot be ruled out.

Evolución de distintos marcadores del remodelado óseo en pacientes hiperparatiroideos sometidos a exéresis quirúrgica de la glándula paratiroides

El exceso de paratirina (PTH) en el hiperparatiroidismo primario (HPTP) provoca un aumento del remodelado óseo con pérdida de densidad mineral en el hueso. El presente estudio pretende evaluar la evoluctón de distintos Marcadores del remodelado óseo (MRO): fosfatasa alcalina (FA) y osteocalcina...

Mediterranean diet and risk of endometrial cancer: a pooled analysis of three italian case-control studies.

BACKGROUND: Some components of the Mediterranean diet have favourable effects on endometrial cancer, and the Mediterranean diet as a whole has been shown to have a beneficial role on various neoplasms. METHODS: We analysed this issue pooling data from three case-control studies carried out between 1983 and 2006 in various Italian areas and in the Swiss Canton of Vaud. Cases were 1411 women with incident, histologically confirmed endometrial cancer, and controls were 3668 patients in hospital for acute diseases. We measured the adherence to the Mediterranean diet using a Mediterranean Diet Score (MDS), based on the nine dietary components characteristics of this diet, that is, high intake of vegetables, fruits/nuts, cereals, legumes, fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) for increasing levels of the MDS (varying from 0, no adherence, to 9, maximum adherence) using multiple logistic regression models, adjusted for major confounding factors. RESULTS: The adjusted OR for a 6-9 components of the MDS (high adherence) compared with 0-3 (low adherence) was 0.43 (95% CI 0.34-0.56). The OR for an increment of one component of MDS diet was 0.84 (95% CI 0.80-0.88). The association was consistent in strata of various covariates, although somewhat stronger in older women, in never oral contraceptive users and in hormone-replacement therapy users. CONCLUSIONS: Our study provides evidence for a beneficial role of the Mediterranean diet on endometrial cancer risk, suggesting a favourable effect of a combination of foods rich in antioxidants, fibres, phytochemicals, and unsaturated fatty acids.

Endometrial cancer and oral contraceptives : an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies.

BACKGROUND: Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors. METHODS: Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy. FINDINGS: The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0·69, 95% CI 0·66-0·71) than sarcomas (0·83, 0·67-1·04; case-case comparison: p=0·02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2·3 to 1·3 per 100 women. INTERPRETATION: Use of oral contraceptives confers long-term protection against endometrial cancer. These results suggest that, in developed countries, about 400 000 cases of endometrial cancer before the age of 75 years have been prevented over the past 50 years (1965-2014) by oral contraceptives, including 200 000 in the past decade (2005-14). FUNDING: Medical Research Council, Cancer Research UK.

Análise microscópica do efeito da radioterapia fracionada em glândula submandibular de rato

OBJETIVO: O estudo teve por objetivo avaliar, quantitativamente, as alterações histológicas induzidas pela radioterapia sobre o parênquima e o estroma da glândula submandibular. MATERIAIS E MÉTODOS: A amostra foi constituída por 30 ratos Wistar, distribuídos em dois grupos: teste e controle. Os 15 animais do grupo-teste foram submetidos a radioterapia da região de cabeça e pescoço, na modalidade fracionada rotacional por cobalto-60, na dose de 60 Gy, realizada em frações de 2 Gy diários, por seis semanas. Decorridas 60 horas da conclusão da radioterapia, as glândulas submandibulares dos animais de ambos os grupos foram excisadas, processadas pela técnica da parafina, coradas com hematoxilina e eosina e analisadas à microscopia óptica. O volume proporcional médio correspondente ao parênquima e ao estroma glandulares foi obtido pelo método estereológico de contagem manual de pontos. RESULTADOS: O volume proporcional de ácinos no grupo irradiado (60,67% ± 6,43) foi significativamente menor que no grupo-controle (67,42% ± 10,90) (p = 0,048), entretanto, não houve diferença estatisticamente significativa entre os grupos para as variáveis parênquima, ductos e estroma (teste t de Student, p > 0,05). CONCLUSÃO: O esquema radioterápico empregado provocou atrofia acinar da glândula submandibular, sem, no entanto, ocorrer alteração quantitativa total do estroma ou do parênquima.

Modelling body mass index and endometrial cancer risk in a pooled-analysis of three case-control studies.

OBJECTIVE: To quantify the relation between body mass index (BMI) and endometrial cancer risk, and to describe the shape of such a relation. DESIGN: Pooled analysis of three hospital-based case-control studies. SETTING: Italy and Switzerland. POPULATION: A total of 1449 women with endometrial cancer and 3811 controls. METHODS: Multivariate odds ratios (OR) and 95% confidence intervals (95% CI) were obtained from logistic regression models. The shape of the relation was determined using a class of flexible regression models. MAIN OUTCOME MEASURE: The relation of BMI with endometrial cancer. RESULTS: Compared with women with BMI 18.5 to <25 kg/m(2) , the odds ratio was 5.73 (95% CI 4.28-7.68) for women with a BMI ≥35 kg/m(2) . The odds ratios were 1.10 (95% CI 1.09-1.12) and 1.63 (95% CI 1.52-1.75) respectively for an increment of BMI of 1 and 5 units. The relation was stronger in never-users of oral contraceptives (OR 3.35, 95% CI 2.78-4.03, for BMI ≥30 versus <25 kg/m(2) ) than in users (OR 1.22, 95% CI 0.56-2.67), and in women with diabetes (OR 8.10, 95% CI 4.10-16.01, for BMI ≥30 versus <25 kg/m(2) ) than in those without diabetes (OR 2.95, 95% CI 2.44-3.56). The relation was best fitted by a cubic model, although after the exclusion of the 5% upper and lower tails, it was best fitted by a linear model. CONCLUSIONS: The results of this study confirm a role of elevated BMI in the aetiology of endometrial cancer and suggest that the risk in obese women increases in a cubic nonlinear fashion. The relation was stronger in never-users of oral contraceptives and in women with diabetes. TWEETABLE ABSTRACT: Risk of endometrial cancer increases with elevated body weight in a cubic nonlinear fashion.

Composição química da glândula abdominal da fêmea da mariposa Castnia licus (Drury) (Lepidoptera:Castniidae): possíveis feromônios e precursores

The hexane and methanolic extracts from pheromonal glands of Castnia licus (Drury) virgin females have been studied. Analyses by gas chromatography and mass spectrometry allowed us to determine the major constituents present in the hexane extract as n-alkanes C21 to C30, (Z)-9-hexadecenoic acid (C16), and (Z)-9-octadecenoic acid (C18) and hexadecanoic acid (C16). Aldehyds, alkenes and acetates were also detected in low concentrations in the extracts. Female pheromone glands were analysed for pheromone precursors using the methanolic extract. In addition to the compounds methyl hexadecanoate and methyl (Z)-9-octadecenoate, the glandular tissue contains a homologous series of methyl esters from C12 to C24. The hexane extract of the female abdomenal glands elicited activity from males in a behavioural bioassay.

Validade da punção biópsia por agulha fina nas doenças da glândula parótida

OBJETIVO: Avaliar o método de punção biópsia aspirativa por agulha fina (PBAAF), técnica relativamente simples, de conhecida importância em cirurgia de cabeça e pescoço. Sua indicação em doenças das glândulas salivares, no entanto, especialmente na parótida, ainda é muito controversa na literatura. O diagnóstico pela PBAAF permite o adequado planejamento terapêutico e preparo do paciente. Muitos, porém, alegam que seu emprego acrescenta muito pouco à conduta terapêutica, além de ser procedimento doloroso e elevar o custo do tratamento. MÉTODO: Os autores analisaram os prontuários de 247 pacientes submetidos a parotidectomias, realizadas entre 1986 e 1998, comparando a punção aspirativa por agulha fina com o anatomopatológico definitivo. Isso foi possível em 211 casos. Houve predomínio do sexo feminino, com idade variando de dez a 84 anos. RESULTADOS: Os tumores benignos foram os mais prevalentes, correspondendo a 85,3% dos casos, com predomínio do adenoma pleomórfico. A punção por agulha fina permitiu diferenciar tumores benignos de malignos em 165 casos (78,1%) e acertou o diagnóstico histológico em 77,6 %. CONCLUSÕES: Concluímos que a PBAAF é um método eficiente e simples que fornece ao cirurgião diagnóstico das neoplasias na grande maioria das vezes e deve fazer parte, sempre que possível, da documentação pré-operatória.

Carcinoma papilífero de alto risco da glândula tireóide: influência dos fatores prognósticos em 126 pacientes

OBJETIVO: Este trabalho tem como objetivo avaliar a influência dos fatores prognósticos em portadores de carcinoma papilífero da tireóide, tratados no Hospital do Câncer (INCA-RJ). MÉTODO: Com base em testes estatísticos (Wilcoxon e Cox) foram analisados 126 prontuários de pacientes atendidos no período de 1986 a 1994, portadores de carcinoma papilífero da tireóide, pertencentes ao grupo de alto risco, segundo os fatores de risco do carcinoma diferenciado da tireóide, considerando uma sobrevida de dez anos livre de doença. RESULTADOS: Observou-se que 104 pacientes eram mulheres (83%); a idade variou de sete a 79 anos, média de 40 anos; invasão capsular ocorreu em 15% (18/126); houve metástase regional em 38% (47/126) e metástase a distância em 11% (13/126). A sobrevida em dez anos livre de doença foi de 81% para os pacientes com menos de 45 anos, e de 76% para os mais idosos: p = 0,0008 (análise univariada) e p = 0,01 (análise multivariada). Dos pacientes que tinham invasão capsular, 72% viveram dez anos, assim como 60% dos que tinham metástase regional, e 28% dos que apresentavam metástase a distância. CONCLUSÕES: A utilização dos fatores de risco no carcinoma papilífero da tireóide é válida mesmo para doença avançada, sendo também de grande importância na projeção do prognóstico e do futuro desenvolvimento da doença.

Conduta conservadora no carcinoma papilífero da glândula tireóide

OBJETIVO: Avaliar os resultados do tratamento do carcinoma papilífero limitado a um lobo da glândula tireóide, através de tireoidectomia parcial com seguimento superior a cinco anos. MÉTODO: Estudo retrospectivo de 105 prontuários de pacientes portadores de carcinoma diferenciado da glândula tireóidea operados no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital Heliópolis, Hosphel, São Paulo de 1977 a 1997 e selecionados 31 casos que apresentavam nódulos limitados a um lobo da glândula com seguimento superior a cinco anos e submetidos à lobectomia total mais istmectomia. RESULTADOS: Observamos somente um caso (3%) de disfonia transitória com paresia de prega vocal unilateral que regrediu espontaneamente. Não houve casos de hipoparatireoidismo transitório ou definitivo. O seguimento médio foi de 12,6 anos, sendo todos com seguimento superior a cinco anos; 10 casos (32%) com seguimento entre 10 e 15 anos e 10 casos (32%) com seguimento além de 15 anos. Não foram observados casos com recorrência loco-regional ou metástase à distância, estando todos eles assintomáticos e sem doença. CONCLUSÃO: Nesta série, a tireoidectomia parcial para carcinoma papilífero limitado a um lobo, mostrou-se eficaz.