Decidual macrophages (DM) are the second most abundant population in the fetal-maternal interface. Their role has been so far identified as being local immuno-modulators favoring the maternal ...tolerance to the fetus. Herein we investigated tissue samples from 11 cases of spontaneous miscarriages and from 9 cases of elective terminations of pregnancy. Using immunohistochemistry and dual immunofluorescence we have demonstrated that in spontaneous miscarriages the DM are significantly increased. Additionally, we noted a significant up-regulation of macrophage FasL expression. Our results further support a dual role for DM during pregnancy and miscarriages. We hypothesize that the baseline DM population in normal pregnancy is in line with an M2 phenotype supporting the ongoing gestation. In contrast, during spontaneous miscarriages, the increased FasL-expressing population could be a part of an M1 phenotype participating in Fas/FasL-related apoptosis. Our results highlight a new aspect of macrophage biology in pregnancy physiology and pathophysiology. Further studies with larger samples are needed to verify the current results and evaluate their clinical impact.
Introduction
Due to technical improvements and growing experience, hysterectomies are performed laparoscopically more and more frequently. We analyzed 43 total laparoscopic hysterectomies (TLH) of ...the years 2005 and 2006 and compared them with 87 vaginal (VH) and 103 abdominal hysterectomies (AH).
Methods
Patients’ original files and surgery reports of the TLHs, VHs and AHs were analyzed retrospectively for the indication of surgery, patients’ age, weight, parity, time for surgery, uterus weight, blood loss, post-operative need of analgetics, hospital stay, complications and so on. Data were compared with Student’s
t
test and χ
2
test.
Results
Indications for TLH were fibroids (
n
= 21), endometrial cancer (
n
= 10), bleeding anomalies (
n
= 7), dysplasia of the cervix uteri (
n
= 3) and others. In 23/43 cases salpingo-ovarectomy was added, in six cases laparoscopic pelvic or paraaortic lymphadenectomy (LNE) was performed. Looking at cases without LNE, patients’ median age was 46 years (32–72), median weight 68 kg (53–115), median time for TLH 130 min (75–270), median uterus weight 150 g (44–954), median blood loss 200 ml (50–600), post-operative analgetica were given for 1.5 days (0–12), and post-operative hospital stay was 6 days (2–15). Indications for VH were genital prolapse (
n
= 53, 61%), often combined with fixative procedures (
n
= 50). In this group, median age was significantly higher (median 56 years,
P
< 0.001). VH was the fastest (median 90 min,
P
< 0.001), but blood loss was highest (median 300 ml,
P
= 0.07). In cases with AH, uterus weight was significantly higher (median 290 g,
P
< 0.001), as well as the need for analgetics (median 4 days,
P
= 0.001), and the hospital stay was longest (median 8 days,
P
< 0.001). Major complications of TLH were bladder injury (3×), of VH rectum lesion (2×, both at pelvic repair measures), of AH post-operative ileus (2×) and vesico-vaginal fistula (1×).
Conclusion
For many patients TLH is a safe and less invasive alternative, especially towards AH, and shows significantly better post-operative reconstitution. Although VH is faster and shows comparable post-operative results, TLH offers the advantage to view the intra-abdominal situs and perform additional steps in case of pathologies.
Mammographic screening and management of breast cancer (BC) in elderly women are controversial and continue to be an important health problem. To investigate, through members of the Senologic ...International Society (SIS), the current global practices in BC in elderly women, highlighting topics of debate and suggesting perspectives.
The questionnaire was sent to the SIS network and included 55 questions on definitions of an elderly woman, BC epidemiology, screening, clinical and pathological characteristics, therapeutic management in elderly women, onco-geriatric assessment and perspectives.
Twenty-eight respondents from 21 countries and six continents, representing a population of 2.86 billion, completed and submitted the survey. Most respondents considered women 70 years and older to be elderly. In most countries, BC was often diagnosed at an advanced stage compared to younger women, and age-related mortality was high. For this reason, participants recommended that personalized screening be continued in elderly women with a long life expectancy.In addition, this survey highlighted that geriatric frailty assessment tools and comprehensive geriatric evaluations needed to be used more and should be developed to avoid undertreatment. Similarly, multidisciplinary meetings dedicated to elderly women with BC should be encouraged to avoid under- and over-treatment and to increase their participation in clinical trials.
Due to increased life expectancy, BC in elderly women will become a more important field in public health. Therefore, screening, personalized treatment, and comprehensive geriatric assessment should be the cornerstones of future practice to avoid the current excess of age-related mortality. This survey described, through members of the SIS, a global picture of current international practices in BC in elderly women.
Abstract Inhibins are dimeric glycoproteins, composed of an alpha-subunit (inhibin-α) and one of two possible beta-subunits (βA or βB), with substantial roles in human reproduction and in ...endocrine-responsive tumours. The aims of this study were to determine the distribution of inhibin-α, -βA and -βB subunits in malignant human endometrial tissue and the assessment of an association with specific clinicopathologic tumour features and clinical outcome. A series of 302 endometrial cancer tissue samples were immunohistochemically analysed with monoclonal antibodies against inhibin subunits. The inhibin-α subunit showed a significant association with histological grading, surgical staging, lymph node status and diabetes in patients with endometrial cancer. Interestingly, loss of inhibin-α expression resulted in a poorer survival of endometrial cancer patients. Additionally, survival analysis demonstrated that inhibin-α immunoreactivity was an independent prognostic factor for progression-free survival, cause-specific survival as well as for overall survival. In contrast, although inhibin-βA- and -βB subunits showed a significant association between endometrial histological subtypes and histological grading, both subunits were not found to be associated with survival in endometrial cancer patients. Therefore, inhibin-α immunostaining might be used as a simple and efficient marker to identify high-risk patients leading to the selection of patients for an aggressive adjuvant therapy.
During surgery for endometrial cancer, a pelvic lymphadenectomy with or without para-aortic lymphadenectomy is performed at least in patients with risk factors (stage I, grading 2 and/or histological ...subtypes with higher risk of lymphatic spread), and is hence recommended by the International Federation of Obstetrics and Gynecology (FIGO). Although lymph node metastases are important prognostic parameters, it has been contentious whether a pelvic lymph node dissection itself has a prognostic impact in the treatment of endometrial cancer, especially in endometrioid adenocarcinoma. Therefore, this study evaluated whether lymphadenectomy has a prognostic impact in patients with endometrioid adenocarcinoma.
The benefits of lymphadenectomy were examined in 214 patients with a histological diagnosis of endometrial adenocarcinoma. Tumour characteristics were analysed with respect to the surgical and pathological stage.
Of the 214 patients with endometrial adenocarcinoma, 171 (79.9%) were classified as FIGO stage I, 15 (7.0%) FIGO stage II, 21 (9.8%) FIGO stage III and 7 (3.3%) FIGO stage IV. One hundred and thirty four (62.6%) of the patients had a histological grade 1 tumour, while 56 (26.2%) and 24 (11.2%) had a histological grade 2 or grade 3 tumour, respectively. Lymphadenectomy was performed in 151 (70.6%) patients. Only 11 (5.1%) patients showed metastatic disease in the lymph nodes. The performance of a lymphadenectomy resulted in significantly increased cause-specific and overall survival, while progression-free survival was not affected by this operative procedure.
The performance of an operative lymphadenectomy resulted in better survival of patients with endometrioid adenocarcinoma. This increase was significant for cause-specific and overall survival, while there was a tendency only towards increased progression-free survival. Therefore, even in endometrioid adenocarcinoma, a pelvic and/or para-aortic lymphadenectomy should be performed.
Anti-Her-2 treatment is successfully administered to Her-2 overexpressing breast cancer patients and significantly implicates upon their survival. Building on these promising results, anti-Her-2 ...treatment protocols were tested as an option for epithelial ovarian cancer (EOC) as well. However Her-2 signalling is known to be modulated by G-protein coupled receptors (GPCR). Since a common GPCR in ovarian cancer is the FSH receptor (FSHR), we investigated the prognostic significance of Her-2 in patients that had been stratified according to their FSHR status.
A total number of 153 EOC patients were included in this study. Her-2 positivity was assessed using a standard protocol. Intriguingly Her-2 turned out to be an independent prognostic marker for poor overall survival only in those patients that did not express FSHR. This did neither apply for the whole panel nor in case of FSHR co-expression.
We thus conclude that Her-2 can be a negative prognosticator only in FSHR negative EOC cases. Hence by stratifying EOC patients according to their FSHR expression status, we introduce a diagnostic protocol to effectively select EOC patients that would most probably respond to anti-Her-2 treatment. This observation could be of clinical importance in terms of selecting the patient that would most likely benefit from anti-Her-2 treatment.
Uterine fibroids are the commonest uterine benign tumors. A potential mechanism of malignant transformation from leiomyomas to leiomyosarcomas has been described. Tyrosine phosphorylation is a key ...mechanism that controls biological functions, such as proliferation and cell differentiation. The aim of the current study was to evaluate the phosphorylation of epithelial growth factor-receptor (EGFR) in normal myometrium, uterine myomas and uterine leiomyosarcomas. Formalin-fixed paraffin-embedded tissue samples from normal myometrium, leiomyomas and leiomyosarcomas were studied. Samples were immunohistochemically (IHC) assessed using the anti-EGFR phosphorylation of Y845 (pEGFR-Y845) and anti-pEGFR-Y1173 phosphorylation-specific antibodies. IHC staining was evaluated using a semiquantitative score. The expression of pEGFR-Y845 was significantly upregulated in leiomyosarcomas (p < 0.001) compared to leiomyomas and normal myometrium. In contrast, pEGFR-Y1173 did not differ significantly between the three groups of the study. Correlation analysis revealed an overall positive correlation between pEGFR Y845 and mucin 1 (MUC1). Further subgroup analysis within the tumoral group (myomas and leiomyosarcomas) revealed an additional negative correlation between pEGFR Y845 and galectin-3 (gal-3) staining. On the contrary no significant correlation was noted within the non-tumoral group. An upregulated EGFR phosphorylation of Y845 in leiomyosarcomas compared to leiomyomas implicates EGFR activation at this special receptor site. Due to these pEGFR-Y845 variations, it can be postulated that MUC1 interacts with it, whereas gal-3 seems to be cleaved from Y845 phosphorylated EGFR. Further research on this field could focus on differences in EGFR pathways as a potentially advantageous diagnostic tool for investigation of benign and malignant signal transduction processes.
Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated.
Amniotic fluid samples were obtained from 192 ...women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GRO-alpha, MIP1alpha, MIP1beta, Histone, and IP10. Analysis was by Bonferroni correction for multiple comparisons. None of the 15 examined cytokines revealed any differences in expression patterns regarding fetal gender. Significant differences were found in IL-4, IL-10, IL-12, TNF- alpha, GRO-alpha and MIP1-beta with respect to gestational age and in GRO-alpha regarding maternal age.
Cytokines utilized as biomarkers in the diagnosis of intrauterine infections are not influenced in their expression pattern by fetal gender but may vary with respect to maternal age and gestational age.
Altered mucin 1 (MUC1) secretion patterns have been implicated in several cancerous conditions including gastric, colorectal and breast carcinomas. Additionally, an association between the expression ...of MUC1, Thomsen-Friedenreich (TF) antigen, and binding of gal-1 (gal-1) has been proposed. Therefore, the aims of this study were to determine the frequency and tissue distribution of MUC1, TF and gal-1 binding in endometrioid adenocarcinomas.
Endometrial carcinomas diagnosed with only one histological tumor form (endometrioid adenocarcinomas) were obtained from 70 patients and classified according to the WHO grading system (G1 = 50; G2 = 12; G3 = 8). An immunohistochemical analysis was performed with specific antibodies against MUC1 and TF and in addition with biotinylated gal-1, followed by a semiquantitative evaluation and statistical analysis (chi2 test and Spearman's correlation coefficient).
MUC1, TF and gal-1 were observed in human endometrioid adenocarcinomas. The MUC1 and gal-1 immunoreaction increased from G1 to G3, while TF demonstrated a lower intensity in G3 compared to G1, although with no statistical significance. However TF showed a significant correlation with MUC1 (p = 0.019) in G1 and G2 endometrioid adeno-carcinomas, with no observed correlation in G3 tumors. MUC1 and TF demonstrated a significant (p = 0.006 and p = 0.046, respectively) down-regulation in surgically staged FIGO III/IV compared to FIGO I/II. Gal-1 binding was up-regulated in FIGO III/IV although with no statistical significance. Interestingly, there was an association between gal-1 binding and lymphangiosis (p = 0.008).
An immuno-histochemical expression of MUC1 and TF and gal-1 binding was demonstrated in human endometrioid adenocarcinomas. Although no significant expression patterns could be demonstrated within different nuclear grading, TF and MUC1 showed a significant correlation in G1/G2 tumors. Therefore, MUC1 and TF might be associated with endometrial malignant transformation. Additionally, MUC1 and TF were down-regulated in stage III/IV tumors, while a higher binding of gal-1 was observed in stage III/IV tumors, suggesting a substantial role of this antigen in endometrial carcinogenesis. Gal-1 binding was associated with lymphangiosis, which is thought to be a poor prognostic marker in endometrial adenocarcinomas. Therefore, MUC1, TF and galectin might have important roles in endometrial pathogenesis and malignant transformation. However, their utilization as specific tumor markers remains unclear and further studies are warranted.
Following breast-conserving surgery or mastectomy followed by autologous breast reconstruction, breast cancer patients were studied to discover their satisfaction with the aesthetic results of the ...two treatment strategies.
One hundred and thirty-four breast cancer patients were included in this study. Sixty-four underwent breast-conserving surgery followed by radiotherapy. Mastectomy was performed in 70 patients with immediate or late reconstruction. To evaluate the quality of the aesthetic results in both groups we designed a questionnaire assessing different cosmetic categories.
Patients in both therapy groups showed a very high satisfaction with their cosmetic results; the patients undergoing breast reconstruction were even more satisfied than the patients who had breast-conserving therapy.
Our study demonstrated that breast reconstruction with autologous tissue offers an opportunity to support patients with advanced breast cancer who were confronted with mastectomy, showing a high degree of satisfaction with the cosmetic results.
PDF
