The amount of preoperative endometrial tissue surface in relation to final endometrial cancer classification.

OBJECTIVE: To evaluate whether the amount of preoperative endometrial tissue surface is related to the degree of concordance with final low- and high-grade endometrial cancer (EC). In addition, to determine whether discordance is influenced by sampling method and impacts outcome. METHODS: A retrospective cohort study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC). Surface of preoperative endometrial tissue samples was digitally calculated using ImageJ. Tumor samples were classified into low-grade (grade 1-2 endometrioid EC (EEC)) and high-grade (grade 3 EEC + non-endometroid EC). RESULTS: The study cohort included 573 tumor samples. Overall concordance between pre- and postoperative diagnosis was 60.0%, and 88.8% when classified into low- and high-grade EC. Upgrading (preoperative low-grade, postoperative high-grade EC) was found in 7.8% and downgrading (preoperative high-grade, postoperative low-grade EC) in 26.7%. The median endometrial tissue surface was significantly lower in concordant diagnoses when compared to discordant diagnoses, respectively 18.7 mm2 and 23.5 mm2 (P = 0.022). Sampling method did not influence the concordance in tumor classification. Patients with preoperative high-grade and postoperative low-grade showed significant lower DSS compared to patients with concordant low-grade EC (P = 0.039). CONCLUSION: The amount of preoperative endometrial tissue surface was inversely related to the degree of concordance with final tumor low- and high-grade. Obtaining higher amount of preoperative endometrial tissue surface does not increase the concordance between pre- and postoperative low- and high-grade diagnosis in EC. Awareness of clinically relevant down- and upgrading is crucial to reduce subsequent over- or undertreatment with impact on outcome.

Immunohistochemical biomarkers are prognostic relevant in addition to the ESMO-ESGO-ESTRO risk classification in endometrial cancer.

OBJECTIVE: Pre-operative immunohistochemical (IHC) biomarkers are not incorporated in endometrial cancer (EC) risk classification. We aim to investigate the added prognostic relevance of IHC biomarkers to the ESMO-ESGO-ESTRO risk classification and lymph node (LN) status in EC. METHODS: Retrospective multicenter study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), analyzing pre-operative IHC expression of p53, L1 cell-adhesion molecule (L1CAM), estrogen receptor (ER) and progesterone receptor (PR), and relate to ESMO-ESGO-ESTRO risk groups, LN status and outcome. RESULTS: A total of 763 EC patients were included with a median follow-up of 5.5-years. Abnormal IHC expression was present for p53 in 112 (14.7%), L1CAM in 79 (10.4%), ER- in 76 (10.0%), and PR- in 138 (18.1%) patients. Abnormal expression of p53/L1CAM/ER/PR was significantly related with higher risk classification groups, and combined associated with the worst outcome within the 'high and advanced/metastatic' risk group. In multivariate analysis p53-abn, ER/PR- and ESMO-ESGO-ESTRO 'high and advanced/metastatic' were independently associated with reduced disease-specific survival (DSS). Patients with abnormal IHC expression and lymph node metastasis (LNM) had the worst outcome. Patients with LNM and normal IHC expression had comparable outcome with patients without LNM and abnormal IHC expression. CONCLUSION: The use of pre-operative IHC biomarkers has important prognostic relevance in addition to the ESMO-ESGO-ESTRO risk classification and in addition to LN status. For daily clinical practice, p53/L1CAM/ER/PR expression could serve as indicator for surgical staging and refine selective adjuvant treatment by incorporation into the ESMO-ESGO-ESTRO risk classification.

[Early postoperative intraocular pressure after phacoemulsification: Normal patients versus glaucoma patients]. / Pression intraoculaire en postopératoire précoce de phakoémulsification chez le sujet normal et glaucomateux.

OBJECTIVE: To compare intraocular pressure (IOP) during the first month following cataract surgery among patients with primary open-angle glaucoma (POAG) and non-glaucomatous patients. MATERIALS AND METHODS: This longitudinal observational study included 19 glaucoma patients and 18 healthy patients scheduled for phacoemulsification with IOL implantation between December 2013 and April 2014. IOP was measured preoperatively, on the day of surgery (j0), the next day (j1), one week (j7) and one month after (M1). The usual antiglaucoma medications were continued without any modification compared to the preoperative medications. Oral treatment with a carbonic anhydrase inhibitor was initiated in the case of ocular hypertension above 30mmHg. RESULTS: IOP in glaucoma patients was 18.42 and 21.16mmHg respectively at j0 and j1 versus 12.94 and 13.78mmHg in non-glaucomatous patients. The difference was significant with P=0.05. There was also more ocular hypertension over 30mmHg in the POAG group (31.5% vs. none in the non-glaucomatous group, P<0.05). CONCLUSION: Glaucoma patients, even stabilized on topical medications, are more likely to experience IOP spikes immediately after uncomplicated cataract surgery. High risk patients should have closer monitoring with IOP measurement the day of or the day after surgery. Further studies are needed to evaluate the effectiveness of prophylactic anti-hypertensive treatment.

Simultaneous treatment with statins and aspirin reduces the risk of prostate cancer detection and tumorigenic properties in prostate cancer cell lines.

Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467-0.812), P<0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068-3.155), P=0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894-4.939), P<0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effects in vitro are enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence.

Comparison of robotic-assisted vs conventional laparoscopy for extraperitoneal paraaortic lymphadenectomy.

OBJECTIVE: To evaluate the perioperative outcomes of robotic-assisted extraperitoneal paraaortic lymphadenectomy for locally advanced cervical cancer and to compare to a previous series of patients from our institution undergoing the same procedure by conventional laparoscopy. METHODS: 17 patients with locally advanced cervical cancer (FIGO stages IB2, IIA2 and IIB-IVA) underwent pretherapeutic extraperitoneal paraaortic lymphadenectomy by robotic-assisted laparoscopy. Perioperative outcomes including age, BMI, FIGO stage, operating time, blood loss, complications and length of hospital stay were compared to a series of 83 patients from our institution undergoing the same procedure by conventional laparoscopy. RESULTS: The median values for operating time and hospital days for the robotic-assisted and conventional laparoscopy groups were 150 vs. 150 min and 2 vs 2 days, respectively. In the robotic group, blood loss was lower (90 vs 20 ml, p<0.05) and more aortic nodes were removed (14 vs 17 nodes, p<0.05). Docking time was 7 min (range 3-15). There were no intraoperative complications. There were no differences for postoperative complications (17.6% vs 8.4%). CONCLUSION: Robotic-assisted and conventional laparoscopy provide similar perioperative outcomes other than lower blood loss and higher number of aortic nodes removed (both without clinical impact) in robotic patients for the performance of extraperitoneal paraaortic lymphadenectomy in patients with locally advanced cervical cancer. We believe that robotic surgery is an additional tool to perform the same surgical procedure. HIGHLIGHTS: Robotic-assisted and conventional laparoscopic extraperitoneal paraaortic lymphadenectomy provide similar perioperative outcomes.

Endometrial carcinoma: molecular alterations involved in tumor development and progression.

In the western world, endometrial carcinoma (EC) is the most common cancer of the female genital tract. The annual incidence has been estimated at 10-20 per 100,000 women. Two clinicopathological variants are recognized: the estrogen related (type I, endometrioid) and the non-estrogen related (type II, non-endometrioid).The clinicopathological differences are paralleled by specific genetic alterations, with type I showing microsatellite instability and mutations in phosphatase and tensin homologue deleted on chromosome 10, PIK3CA, K-RAS and CTNNB1 (ß-catenin), and type II exhibiting TP53 mutations and chromosomal instability. Some non-endometrioid carcinomas probably arise from pre-existing endometrioid carcinomas as a result of tumor progression and, not surprisingly, some tumors exhibit combined or mixed features at the clinical, pathological and molecular levels. In EC, apoptosis resistance may have a role in tumor progression. Understanding pathogenesis at the molecular level is essential in identifying biomarkers for successful targeted therapies. In this review, the genetic changes of endometrial carcinogenesis are discussed in the light of the morphological features of the tumors and their precursors.

The EMT signaling pathways in endometrial carcinoma

Endometrial cancer (EC) is the most common gynecologic malignancy of the female genital tract and the fourth most common neoplasia in women. In EC, myometrial invasion is considered one of the most important prognostic factors. For this process to occur, epithelial tumor cells need to undergo an epithelial to mesenchymal transition (EMT), either transiently or stably, and to differing degrees. This process has been extensively described in other types of cancer but has been poorly studied in EC. In this review, several features of EMT and the main molecular pathways responsible for triggering this process are investigated in relation to EC. The most common hallmarks of EMT have been found in EC, either at the level of E-cadherin loss or at the induction of its repressors, as well as other molecular alterations consistent with the mesenchymal phenotype-like L1CAM and BMI-1 up-regulation. Pathways including progesterone receptor, TGFβ, ETV5 and microRNAs are deeply related to the EMT process in EC (AU)

ETV5 cooperates with LPP as a sensor of extracellular signals and promotes EMT in endometrial carcinomas.

Endometrial carcinoma (EC) is the most frequent among infiltrating tumors of the female genital tract, with myometrial invasion representing an increase in the rate of recurrences and a decrease in survival. We have previously described ETV5 transcription factor associated with myometrial infiltration in human ECs. In this work, we further investigated ETV5 orchestrating downstream effects to confer the tumor the invasive capabilities needed to disseminate in the early stages of EC dissemination. Molecular profiling evidenced ETV5 having a direct role on epithelial-to-mesenchymal transition (EMT). In particular, ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell-cell and cell-substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines. Furthermore, we identified the lipoma-preferred partner protein as a regulatory partner of ETV5, acting as a sensor for extracellular signals promoting tumor invasion. All together, we propose ETV5-transcriptional regulation of the EMT process through a crosstalk with the tumor surrounding microenvironment, as a principal event initiating EC invasion.

Review of the complexation of tetravalent actinides by ISA and gluconate under alkaline to hyperalkaline conditions.

Isosaccharinic (ISA) and gluconic acids (GLU) are polyhydroxy carboxylic compounds showing a high affinity to metal complexation. Both organic ligands are expected in the cementitious environments usually considered for the disposal of low- and intermediate-level radioactive wastes. The hyperalkaline conditions imposed by cementitious materials contribute to the formation of ISA through cellulose degradation, whereas GLU is commonly used as a concrete additive. Despite the high stability attributed to ISA/GLU complexes of tetravalent actinides, the number and reliability of available experimental studies is still limited. This work aims at providing a general and comprehensive overview of the state of the art regarding Th, U(IV), Np(IV), and Pu(IV) complexes with ISA and GLU. In the presence of ISA/GLU concentrations in the range 10(-5)-10(-2) M and absence of calcium, An(IV)(OH)x(L)y complexes (An(IV)=Th, U(IV), Np(IV), Pu(IV); L=ISA, GLU) are expected to dominate the aqueous speciation of tetravalent actinides in the alkaline pH range. There is a moderate agreement among their stability, although the stoichiometry of certain An(IV)-GLU complexes is still ill-defined. Under hyperalkaline conditions and presence of calcium, the species CaTh(OH)4(L)2(aq) has been described for both ISA and GLU, and similar complexes may be expected to form with other tetravalent actinides. In the present work, the available thermodynamic data for An(IV)-ISA/GLU complexes have been reviewed and re-calculated to ensure the internal consistency of the stability constants assessed. Further modelling exercises, estimations based on Linear Free-Energy Relationships (LFER) among tetravalent actinides, as well as direct analogies between ISA and GLU complexes have also been performed. This approach has led to the definition of a speciation scheme for the complexes of Th, U(IV), Np(IV) and Pu(IV) with ISA and GLU forming in alkaline to hyperalkaline pH conditions, both in the absence and presence of calcium.

Novel molecular profiles of endometrial cancer-new light through old windows.

Endometrial carcinoma (EC) is the most common gynecological malignancy in the western world. A widely accepted dualistic model, which has been established on a morphological basis, differentiates EC into two broad categories: Type I oestrogen-dependent adenocarcinoma with an endometrioid morphology and Type II non-oestrogen-dependent EC with a serous papillary or clear cell morphology. Molecular genetic evidence indicates that endometrial carcinoma, as described in other malignancies, likely develops as the result of a stepwise accumulation of alterations in cellular regulatory pathways, such as oncogene activation and tumor suppressor gene inactivation, which lead to dysfunctional cell growth. These molecular alterations appear to be specific in Type I and Type II cancers. In type I endometrioid endometrial cancer, PTEN gene silencing in conjunction with defects in DNA mismatch repair genes, as evidenced by the microsatellite instability phenotype, or mutations in the K-ras and/or beta-catenin genes, are recognized major alterations, which define the progression of the normal endometrium to hyperplasia, to endometrial intraepithelial neoplasia, and then on to carcinoma. In contrast, Type II cancers show mutations of TP53 and Her-2/neu and seem to arise from a background of atrophic endometrium. Nevertheless, despite the great effort made to establish a molecularly-based histological classification, the following issues must still be clarified: what triggers the tumor cells to invade the myometrium and what causes vascular or lymphatic dissemination, finally culminating in metastasis? RUNX1, a transcription factor, was recently identified as one of the most highly over-expressed genes in a microarray study of invasive endometrial carcinoma. Another candidate gene, which may be associated with an initial switch to myometrial infiltration, is the transcription factor ETV5/ERM. These studies, as well as those conducted for other genes possibly involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, could help in understanding the differences in the biology and the clinical outcome among histological types.

Molecular determinants of invasion in endometrial cancer.

Endometrial carcinoma is the most common gynaecological malignancy in the western world and the most frequent among infiltrating tumours of the female genital tract. Despite the characterisation of molecular events associated with the development of endometrial carcinoma, those associated with the early steps of infiltration and invasion in endometrial cancer are less known. Deep myometrial invasion correlates with more undifferentiated tumours, lymph-vascular invasion, node affectation and decreased global survival. In this review we present an overview of the molecular pathology of myometrial infiltration that defines the initial steps of invasion in endometrial cancer. Down-regulation of E-cadherin as a main player of epithelial to mesenchymal transition, as well as modifications on other molecules involved in cell-cell contacts, render cells with a migratory phenotype. In addition, altered signalling pathways and transcription factors associate with myometrial invasion, histologic grade and metastasis.

Molecular determinants of invasion in endometrial cancer

Endometrial carcinoma is the most common gynaecological malignancy in the western world and the most frequent among infiltrating tumours of the female genital tract. Despite the characterisation of molecular events associated with the development of endometrial carcinoma, those associated with the early steps of infiltration and invasion in endometrial cancer are less known. Deep myometrial invasion correlates with more undifferentiated tumours, lymph-vascular invasion, node affectation and decreased global survival. In this review we present an overview of the molecular pathology of myometrial infiltration that defines the initial steps of invasion in endometrial cancer. Down-regulation of E-cadherin as a main player of epithelial to mesenchymal transition, as well as modifications on other molecules involved in cell-cell contacts, render cells with a migratory phenotype. In addition, altered signalling pathways and transcription factors associate with myometrial invasion, histologic grade and metastasis (AU)

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