Fewer endometrial abnormalities occurred during 2 years treatment with anastrozole compared with tamoxifen although statistical significance was not reached in this sub-protocol analysis.

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On behalf of The ATAC Trialists' GroupObjective The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial is a randomised, double-blind trial comparing 'Arimidex' (anastrozole), alone or in combination with tamoxifen, relative to tamoxifen alone as a five year adjuvant treatment for postmenopausal women with early breast cancer. Because tamoxifen is associated with endometrial pathology, the ATAC endometrial subprotocol was initiated to establish the background prevalence of pathology, and to assess prospectively the incidence and nature of intrauterine changes before and following endocrine therapy. Setting International.Population and Study Design Two hundred and eighty-five women entered the subprotocol: the mean age was 60 years (range 44-80 years); 113 women (40%) had taken hormone replacement therapy prior to randomisation, and 238 women were parous (84%). The age at onset of the menopause was 32-58 years, with the majority becoming menopausal between 46 and 55 years of age. Two hundred and seventy-two women had a hysteroscopy before they commenced trial medication. Hysteroscopy was performed successfully in 265 women. In six women, failure of hysteroscopy at baseline led to withdrawal from the study. Three of the women who withdrew had a pipelle biopsy taken. Therefore, the total number of endometrial biopsies at baseline was 268. Main outcome measures To assess the demographic characteristics of women entering the endometrial subprotocol and their hysteroscopic and histological findings before commencing trial medication. Results At hysteroscopy, there was a diagnosis of endometrial polyps in 34 women (13%), fibroids in 16 women (6%) and one case of suspicious endometrium, which was confirmed as a polyp on histology. Only 21 of the 34 polyps seen hysteroscopically were proven histologically (62% accuracy of hysteroscopy).Final histology found the prevalence of endometrial diagnostic categories as follows: 123 inactive endometrium (46%), 20 benign polyps (7%), 17 secretory endometrium (6%), 7 proliferative endometrium (3%), 3 atypical hyperplasia (2 in a polyp), 1 simple hyperplasia (in a polyp) and 1 fibroid. The remaining women had pipelle samples with insufficient tissue obtained, indicating a normal endometrial cavity. Conclusion This is the first study of such size in gynaecologically asymptomatic breast cancer patients. This paper describes the findings in individual patients before any trial treatment was given. In this baseline group, 82% (219/268) of women had a normal endometrial cavity; 18% (49/268) had endometrial activity (proliferative or secretory endometrium in 9%) or an intracavity abnormality (hyperplasia, polyps and a fibroid in 9%). In total, 36% of biopsies had insufficient tissue for diagnosis, which in combination with a normal hysteroscopy was classed as normal. The appearance of a polyp hysteroscopically in this group was not proven histologically in approximately 40% of cases. The development of uterine pathology over time in the ATAC study will subsequently be assessed again...

The CXCR7, a new receptor for CXCL12 with higher affinity than CXCR4 has raised key issues on glioma cell migration. The aim of this study is to investigate the CXCR7 mRNA expression in diffuse astrocytomas tissues and to evaluate its interactions with CXCR4 and HIF1α expression and IDH1 mutation. CXCR7, CXCR4 and HIF1α mRNA expression were evaluated in 129 frozen samples of astrocytomas. IDH1 mutation status was analyzed with gene expressions, matched with clinicopathological parameters and overall survival time. Protein expression was analyzed by immunohistochemistry in different grades of astrocytoma and in glioma cell line (U87MG) by confocal microscopy. There was significant difference in the expression levels of the genes studied between astrocytomas and non-neoplasic (NN) controls (p < 0.001). AGII showed no significant correlation between CXCR7/HIF1α (p = 0.548); there was significant correlation between CXCR7/CXCR4 (p = 0.042) and CXCR7/IDH1 (p = 0.008). GBM showed significant correlations between CXCR7/CXCR4 (p = 0.002), CXCR7/IDH1 (p < 0.001) and CXCR7/HIF1α (p = 0.008). HIF1α overexpression was associated with higher expressions of CXCR7 (p = 0.01) and CXCR4 (p < 0.0001), while IDH1 mutation was associated with lower CXCR7 (p = 0.009) and CXCR4 (p = 0.0005) mRNA expressions. Protein expression increased with malignancy and in U87MG cell line was mainly localized in the cellular membrane. CXCR7 was overexpressed in astrocytoma and correlates with CXCR4 and IDH1 in AGII and CXCR4, IDH1 and HIF1α in GBM. Overexpression HIF1α was related with higher expressions of CXCR7 and CXCR4, otherwise IDH1 mutation related with lower expression of both genes. No association between CXCR7 and CXCR4 expression and survival data was related.

A retrospective study of 81 patients with low-grade astrocytoma (LGA) comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS) and progression- free survival (PFS). Degree of tumor resection was classified as gross total resection (GTR), subtotal resection (STR) or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013), whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33). Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.

The presence of pathology was associated with increased endometrial thickness. The relative sensitivity and specificity of hysteroscopy and endometrial thickness for the diagnosis of endometrial pathology was comparable to other studies. If screening of the endometrium prior to treatment is appropriate, this study supports the use of an endometrial thickness of 3 mm, as assessed by TVUS, as a threshold for needing further investigation. This study demonstrates that if the endometrial thickness is >3 mm, hysteroscopy and biopsy is the optimal method of detecting intrauterine pathology in women with breast cancer who are about to commence endocrine treatment.

RationaleRecent data have demonstrated the superiority of Pembroluzimab over chemotherapy for patients with advanced NSCLC and high (≥50% expression) of PD-L1.1 This has resulted in NICE approving Pembroluzimab as a first line treatment option for patients with advanced NSCLC in June 2017. The original trial however excluded patients with PD-L1 testing on EBUS samples. We therefore conducted a large, multicentre study to clarify whether specimens obtained by EBUS-TBNA were suitable for testing PD-L1 in patients with NSCLC.MethodsNSCLC samples acquired by EBUS-TBNA (29.4%), percutaneous biopsy (31.2%), endobronchial biopsy (13.8%), surgical (21.4%) or other techniques (4.1%) were recorded from 435 consecutive patients with known or suspected lung cancer across 5 centres in England between January 2015 and December 2016.ResultsPD-L1 assessment (using the 22 C3 assay in all cases) was possible in 92.2% of patients undergoing EBUS and there was no difference in success of PD-L1 testing according to modality of tissue acquisition (p=0.18). The frequency of complications from EBUS-TBNA was similar to endobronchial or percutaneous techniques but lower than surgical procedures (5.0% vs 13.8%; p=0.03). PD-L1 expression in the cohort was high (≥50%) in 28.5%, weak (≥1%–50%) in 28.2%, whilst 43.3% of patients were PD-L1 negative. The only statistically significant predictor for PD-L1 expression in multivariate analysis was the presence of brain metastasis at diagnosis (OR 2.02; CI 1.04–3.90). 47 patients (11.4%) were treated with immunotherapy and the response rate was 16.2%. All patients that responded to immunotherapy had high (≥50%) expression of PD-L1.ConclusionsThis large multicentre study demonstrates for the first time that samples obtained by EBUS-TBNA in routine practice are suitable for PD-L1 testing in patients with NSCLC. The presence of brain metastases at diagnosis predicts high PD-L1 expression in this cohort and this new finding should be tested in future clinical trials.ReferenceReck M, Rodrguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1Positive NonSmall-Cell Lung Cancer. N Engl J Med 2016;375(19):1823-33. doi:10.1056/NEJMoa1606774

RESUMO IntroduçãoÀ medida que uma massa cresce dentro do espaço craniano, uma proporcional quantidade de líquido cefalorraquidiano é retirada dessa caixa. Nesse período, a pressão intracraniana (PIC) não se eleva. Deveríamos esperar que, quando todo compartimento liquórico fosse extraído de dentro do crânio, a curva que determina a relação entre a PIC e o volume acrescido ao espaço -curva pressão/volume -assumisse um caráter retilíneo, e a PIC fosse aumentando linearmente à medida que a massa continuasse crescendo. Entretanto, tal curva assume um traçado gráfico exponencial denotando uma rápida ascensão da PIC após a fase em que todo o liquor foi expulso do compartimento em questão. Nessa fase de ascensão rápida, pequenos acréscimos de volume causam variações positivas da PIC cada vez maiores para um mesmo volume acrescentado. No caso dos inchaços, reperfusionais ou não, esses acréscimos de volume são volêmicos sanguíneos, ou seja, intravasculares. 1,17,19,20,24,25,27,38 Muito provavelmente, como veremos à frente, tal ascensão exponencial relaciona-se a um acúmulo progressivo de volume sanguíneo intracraniano associado à vasodilatação isquêmica desproporcionalmente grande em relação ao aumento da massa que vem crescendo. Provavelmente, esse aumento de volume sanguíneo é que proporciona o aparecimento da fase exponencial ascendente da curva de Langfitt. Esse acúmulo progressivo de volume sanguíneo encefálico estaria certamente relacionado ao desencadeamento e à persistência da cascata vasodilatadora, já citada em publicações prévias. 1,24,25,27 Curva de Langfitt A curva de Langfitt compreende o traçado que relaciona o eixo da PIC, na vertical, e o eixo do volume que é acrescido à caixa craniana, na horizontal (Figura 1). Nota-se que, no início, o aumento da massa não implica