Spontaneous abortion is associated with differentially expressed angiogenic chemokines in placenta and decidua.

PURPOSE: Miscarriage is one of the most common complications of pregnancy. Although chromosomal abnormalities of the embryo is a well-known cause of miscarriage, a lot of cases remain unexplained, with immunologic and vascular growth alterations being considered as probable causes. Chemokines are produced by a variety of cells and exhibit several functions including both pro and anti-angiogenic properties. In this study, we investigated the role of the angiogenic and angiostatic chemokines in placenta and decidua tissues from spontaneous and induced abortions. METHODS: Total RNA was extracted from the placenta and decidua tissues, which was then purified and converted into cDNA. Real-time PCR was then performed for the expression of the angiogenic CCL2, CCL5, CCL20, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, CXCL8 and CXCL4, and the angiostatic CXCL9, CXCL10, CXCL11, CXCL12 and CXCL14 and results were then statistically analyzed. RESULTS: Regarding the placenta, CXCL7 (2.29-fold, 2.16-2.38, p < 0.05), CXCL4 (1.01-fold, 0.74-4.447, p < 0.05), CXCL9 (0.87-fold, 0.43-1.34, p < 0.05) and CXCL11 (0.31-fold, 0.22-0.45, p < 0.05) were altered in spontaneous abortions. CCL2, CCL5, CXCL2-3, CXCL8, CXCL10, CXCL12 and CXCL14 were not statistically significant altered. Regarding the decidua, CXCL7 (7.13-fold, 6.32-7.54, p < 0.01), CXCL8 (11.02-fold, 8.58-13.45, p < 0.05), CCL20 (1.21-fold, 0.29-1.89, p < 0.05) and CXCL9 (5.49-fold, 3.67-6.39, p < 0.05) were overexpressed in spontaneous abortions. CXCL2-4, CCL2, CCL5, CXCL10-12 and CXCL14 did not show any differences. The expression of the chemokines CXCL1, CXCL5-6 was absent in either tissue or group. CONCLUSION: Our results show that the overexpression of angiostatic and diminished expression of angiogenic chemokines takes place in the placenta and decidua of spontaneous abortions, suggesting that dysregulation of angiogenesis could be a contributive factor to the pathogenesis of miscarriage.

Imbalance of growth factors mRNA expression associated with oxidative stress in the early pregnancy loss.

OBJECTIVE: The aim of this study was to examine the role of growth factors associated with angiogenesis and oxidative stress in the pathogenesis of spontaneous miscarriage. METHODS: We performed a comparative mRNA expression analysis of VEGF, PlGF, Flt-1, Angiogenin and Endoglin using Real-Time PCR, in the placenta and decidua collected from 12 patients presenting with spontaneous abortion and from 14 women undergoing induced abortion, during the first and second trimester of pregnancy. RESULTS: The mRNA expression of Flt-1 was significantly upregulated in the placenta of spontaneous abortions (5.17-fold, IQR: 2.72-9.11, p < 0.01). The placental expression of the soluble isoforms of Flt-1, sFlt-1 e15a and sFlt-1 i13, was also significantly upregulated in spontaneous abortions (sFlt-1 e15a: 2.35-fold, IQR: 0.98-2.83, p < 0.01; sFlt-1 i13: 3.47-fold, IQR: 2.37-5.08, p < 0,05). Placental tmFlt-1, PlGF and Endoglin showed a tendency of higher expression levels in spontaneous abortions, although they did not reach statistical significance (tmFlt-1: 7.42-fold, IQR: 3.58-14.32; PlGF: 2.36-fold, IQR: 0.90-4.12; Endoglin: 1.97-fold, IQR: 1.18-2.43). VEGF and Angiogenin mRNA expression in induced, as well as in spontaneous abortions, did not convey any statistically significant difference. In the decidua, the expression levels of Flt-1 and its splice variants sFlt-1 e15a, sFlt-1 i13 and tmFlt-1 did not show any statistically significant differences, as was the case for the rest of the herein examined growth factors. CONCLUSIONS: In this study, we observed higher levels of sFlt-1 mRNA expression in the placenta of spontaneous abortions, while expression of other growth factors in placenta and decidua remained constant. This suggests that an imbalance of sFlt-1 expression in the placenta might contribute to the pathogenesis of spontaneous abortion, probably via oxidative stress, providing a possible biomarker for prompt identification of this condition.

Investigating the impact of different strategies for endometrial preparation in frozen cycles considering normal responders undergoing IVF/ICSI cycles: a multicenter retrospective cohort study.

Uncertainty exists concerning the type, adjunct, or dose of regimen to offer in frozen cycles in infertile women undergoing IVF/ICSI. Current systematic reviews have failed to identify one method of endometrial preparation as being more effective than another, whereas many IVF Units use variable and mixed protocols mainly based on their experience and convenience of use. Thus, we performed a four-center two-arm retrospective cohort study, encompassing 439 cycles in 311 women. The modalities analyzed were: Modified natural cycle without and with luteal support (Groups 1,2) and Hormone Replacement cycle (HRC) with and without GnRHa suppression (Groups 3,4). Various schemes of progesterone and estradiol were used and compared. χ2 tests for categorical data and t-tests for continuous data were employed, stratifying by exposure, along with univariate and multivariable Logistic Regression models and subgroup analyses, according to the number of embryos transferred (1 vs. ≥2) and day of transfer (d2 vs. d5). Group 3 presented with statistically significant higher live birth and miscarriage rates in comparison to Group 4 (RR = 5.87, 95%CI: 2.44-14.14 and RR = 0.19, 95%CI: 0.06-0.60, respectively), findings that persisted in subgroup analyses according to the day of transfer and the number of embryos transferred. Progesterone administration through the combination of vaginal tabs and gel was associated with lower clinical pregnancy rates when compared to tabs (RR = 0.19, 95%CI: 0.05-0.71). The stable estrogen protocol compared to increasing estrogen at day 5 was associated with a higher positive hCG test and clinical pregnancy rate, while the progesterone through vaginal tabs was linked with lower miscarriages compared either with gel or combinations. In conclusion, HRC with GnRHa appears to be superior to HRC without GnRHa, concerning live birth and miscarriage, especially when the number of embryos transferred are ≥2 and irrespective of day of transfer. The use of progesterone vaginal tabs compared to gel or combinations is associated with better outcomes. Age is a significant predictor of a negative hCG test and clinical pregnancy rates. A properly conducted RCT is needed to evaluate the optimal frozen embryo transfer preparation strategy.Abbreviations: SD: standard deviation; BMI: body mass index; PCOS: polycystic ovarian syndrome; IQR: interquartile range; FSH: follicle-stimulating hormone; LH: luteinizing hormone; TSH: thyroid-stimulating hormone.

Significance of changes in inflammatory parameters following uterine artery embolization in pre-menopausal females.

The purpose of the present study was to describe the course of changes in laboratory inflammatory markers following bilateral uterine artery embolization (UAE) as a treatment for leiomyomas and adenomyosis. The body temperature was measured and blood samples were collected to determine white blood cell (WBC) count and C-reactive protein (CRP) levels in 270 patients on the day prior to UAE and for up to 4 days post-embolization. Aside from a single case with a non-inflammatory complication, none of the other cases had any complications. Post-UAE leukocytosis with a mean maximum value of 10.8±3.5x109/l (range, 5.9-18.6x109/l) was observed one-year post-intervention. The mean leukocyte numbers were indicated to be higher on day 3 post-UAE. The CRP level was also increased post-UAE, with a mean maximum value of 7.75±3.5 mg/dl. Maximum levels were reached in 8 patients on the 2nd and in 11 patients on the 3rd post-operative day. The maximum pain score was ~5.5 and reached its lowest level at the end of the 12th week post-intervention. The present study did not consider an association between the embolic material used or uterus size with the level of treatment success. No complications were observed post-UAE; however, a significant increase in the WBC count was observed within the first 3 days, indicating mild leukocytosis.

Blood groups type linked to breast cancer in a Greek cohort of women - a case control study.

PURPOSE: To investigate the possible association between ABO blood types and breast cancer in Greek women. METHODS: 202 female patients with breast cancer and 139 healthy women as control group were examined clinically and with breast ultrasound and those older than 40 years, also with bilateral digital mammography. RESULTS: In the case-group, 26.7% had blood group O, 5.5% had blood group B, 61.9% had blood group A and 5.9% had blood group AB. In the control-group, 47.5% had blood group O, 13.7% had blood group B, 31.6% had blood group A and 7.2% had blood group AB. Usage of diagrams with the percentages of frequency, the average control, Pearson, Spearman, Student's t-tests analyzed with SPSS statistical software showed a significant correlation between breast cancer and blood group A (p<0.01). CONCLUSIONS: Although in the literature it is controversial whether ABO/Rh blood groups have association with breast cancer, the results of our study show a significant correlation between breast cancer and blood group A.

A new risk malignancy index to predict ovarian cancer: a bicentric preliminary study.

PURPOSE: Ovarian cancer is the most common cause of gynecologic cancer death. Considering that diagnosis of ovarian cancer is done in advanced stage in most cases, the purpose of this study was to construct a "new risk malignancy index" (NRMI) to assess the risk of ovarian cancer in women with a pelvic mass. METHODS: The index includes the classical vaginal ultrasound and CA125 tumor marker along with risk and protective factors for ovarian malignancy. RESULTS: Compared to the original Risk Malignancy Index (RMI), NRMI found retrospectively a greater number of patients with ovarian cancer. CONCLUSIONS: NRMI seems to be a promising tool for the early and reliable detection of cases with ovarian malignancy in an effort to maximize surgical benefits.

Administration of low-molecular-weight heparin in patients with two or more unsuccessful IVF/ICSI cycles: a multicenter cohort study.

To compare the effects of the administration of low-molecular-weight heparin (LMWH) in subfertile patients with two or more unsuccessful IVF/ICSI cycles. In this six-center two-arm retrospective cohort study, the study population (230 women) underwent a GnRH-antagonist protocol and was classified into two groups, according to the couse of LMWH or not. Groups were compared regarding the clinical and IVF/ICSI cycle characteristics and reproductive outcomes, whereas clinical pregnancy and miscarriage constituted the primary endpoints. Logistic regression analysis was performed to determine the potential predictors of clinical pregnancy, miscarriage and live birth rates using the Enter method. Baseline characteristics were comparable in the two groups. There was no statistically significant difference between the two study groups with regard neither to clinical pregnancy and miscarriage rates (33/133 vs. 20/97, p = .456 and 15/133 vs. 9/97, p = .624, respectively), nor to the secondary outcomes preset for this study (all p values >.05). Logistic regression revealed that age of the woman and ICSI and dose of gonadotrophins used were predictors of clinical pregnancy and live birth, respectively. In conclusion, there is no evidence to support the standard addition of LMWH in patients with two or more unsuccessful IVF/ICSI cycles.

Ten Years of Experience in Contraception Options for Teenagers in a Family Planning Center in Thrace and Review of the Literature.

Abstract: Introduction: The goal of our study was to investigate and evaluate the contraceptive behavior in teenagers from our family planning centre that services two different religious and socioeconomic populations living in the Thrace area. Methods: During the last 10 years 115 Christian Orthodox (group A) and 53 Muslim teenagers (group B) were enrolled in our retrospective study. Contraceptive practice attitudes were assessed by a questionnaire. Religion, demographics, socio-economic characteristics were key factors used to discuss contraception and avoid unplanned pregnancy in each group and to compare with the contraceptive method used. Results: The most used contraceptive method-about two times more frequently-among Christian Orthodox participants was the oral contraceptive pill (p = 0.015; OR = 1.81, 95% CI = 1.13-2.90), while in the other group the use of condoms and IUDs was seven and three times more frequent, respectively. Our family planning centre was the main source of information for contraception. Conclusions: During adolescence, the existence of a family planning centre and participation in family planning programs plays a crucial role to help the teenagers to improve their knowledge and choose an effective contraception method.

Preoperative assessment in endometrial cancer. Is triage for lymphadenectomy possible?

PURPOSE: We sought to examine whether a preoperative assessment with usual means, available in most hospitals (preoperative histology, pelvic MRI, serum CA-125) can confidently exclude from a full staging surgical procedure low-risk endometrial carcinoma (EC) patients according to ESMO-ESTRO-ESGO criteria (stage I endometrioid EC, grade 1 or 2, myometrial invasion <50% and negative lymphovascular space invasion). METHODS: We retrospectively identified all EC patients that underwent total hysterectomy with bilateral salpingo-oophorectomy (TH-BSO) plus lymph node dissection (LND) as primary treatment for endometrioid tumors from January, 2000 to December, 2010. Extensive review was made through patients' medical records. Having set the final pathology report as the "gold standard", we applied the ESMO-ESGO-ESTRO criteria to classify patients into risk categories (low-risk and non-low risk). We also evaluated preoperative risk status using combined data from preoperative biopsy, pelvic MRI and serum CA-125. We classified patients according to the following criteria: grade 1 or 2 on preoperative histology, myometrial invasion on MRI <50% and serum CA-125 <35 IU/ml, in low risk group. Receiver operating characteristic (ROC) curves were plotted. The area under the ROC curve (AUC), quantifying the overall ability of the combined preoperative assessment to discriminate between patients at low and non-low risk, was the primary outcome of our study. False negative rate was the secondary outcome. RESULTS: Preoperative data on histology, MRI and CA-125 levels were available for 292 patients. The sensitivity and specificity of combined preoperative assessment to discriminate between low- and non-low risk EC patients according to ESMO-ESTRO-ESGO criteria were 96.1% and 73.6% respectively. AUC of the corresponding ROC curve was 0.849. False negative rate was 3.8% (9/235). Among the 9 patients falsely classified as low-risk, one patient had nodal metastasis (1/9, 11.1%) after full staging. CONCLUSION: A selective LND strategy for EC patients based on preoperative assessment is possible and would probably be cost-effective, while not jeopardizing patients' survival or patient quality of life (QoL).

Endometrial injury for RIF patients undergoing IVF/ICSI: a prospective nonrandomized controlled trial.

To evaluate the effect of endometrial injury on clinical outcomes in subfertile women with repeated implantation failures (RIF) undergoing assisted reproduction. In this prospective nonrandomized controlled trial, 103 subfertile women with RIF were included. Fifty-one underwent endometrial injury through hysteroscopy in the early follicular phase of the previous cycle and 52 underwent the standard protocol without any intervention. Live birth and miscarriage were the primary outcomes. Clinical and in vitro fertilization (IVF) cycle characteristics, were also compared between groups. Both groups were comparable in terms of baseline and cycle characteristics. Live birth rates were significantly higher in the study, compared with the control group (18/51 vs. 8/52, odds ratio (OR) = 0.25; 95% confidence interval (CI) = 0.10-0.64; p = 0.020), although miscarriage rates were similar (7/51 vs. 10/52, OR= 0.25; 95%CI= 0.12-0.66; p = 0.452). The rest of the outcomes parameters were comparable between groups. Logistic regression analysis revealed that endometrial injury and duration of subfertility were independent predictors of live birth after control of other variables (OR = 2.818; 95%CI = 1.044-7.605; p = 0.041 and OR = 0.674; 95%CI = 0.461-0.985, p = 0.042, respectively). Endometrial injury induced through office hysteroscopy in the preceding cycle in subfertile women with RIF improves live birth rates.

Cervical cancer: screening, diagnosis and staging.

Purpose: Despite the widespread screening programs, cervical cancer remains the third most common cancer in developing countries. Based on the implementation of cervical screening programs with the referred adoption of improved screening methods in cervical cytology with the knowledge of the important role of the human papilloma virus (HPV) it's incidence is decreased in the developed world. Even if cervical HPV infection is incredibly common, cervical cancer is relatively rare. Depending on the rarity of invasive disease and the improvement of detection of pre-cancerous lesions due to the participation in screening programs, the goal of screening is to detect the cervical lesions early in order to be treated before cancer is developed. In populations with many preventive screening programs, a decrease in cervical cancer mortality of 50-75% is mentioned over the past 50 years. The preventive examination of vagina and cervix smear, Pap test, and the HPV DNA test are remarkable diagnostic tools according to the American Cancer Association guidelines, in the investigation of asymptomatic women and in the follow up of women after the treatment of pre-invasive cervical cancer. The treatment of cervical cancer is based on the FIGO 2009 cervical cancer staging.

The contribution of rapid intraoperative cytology in the evaluation of endometrial cancer spread.

INTRODUCTION: Peritoneal washing cytology and imprint cytology of pelvic lymph nodes samples were used to evaluate the rapid cytologic detection of peritoneal and retroperitoneal spread of endometrial cancer. MATERIALS AND METHODS: We undertook a study on 194 endometrial cancer patients who underwent primary treatment in the Gynecologic Clinic, Democritus University of Thrace. All patients were subjected to peritoneal washing (PW) cytology and imprint cytology performed on lymph node sampling. The cytologic specimens were stained by May-Grünwald Giemsa (MGG) and Haematoxylin eosin (HE) techniques. Cell-blocks prepared from peritoneal washings (PWs) and the lymph node samples were sent for histologic examination. The cytologic fi ndings were correlated to histologic results. RESULTS: Rapid intraoperative cytology provides a useful diagnostic technique for the assessment of endometrial cancer spread. HE and MGG stain presented different values of sensitivity and specifi city in the detection of peritoneal and retroperitoneal spread of endometrial cancer. CONCLUSION: Cytologic assessment of intraperitoneal and retroperitoneal spread of endometrial cancer is a rapid, intraoperative procedure, which provides the surgeon with useful information regarding the stage of the disease and the subsequent therapeutic approach.

Correlation between maternal first trimester plasma leptin levels and birth weight among normotensive and preeclamptic women.

OBJECTIVE: To determine the connection between maternal first trimester serum leptin levels and newborn weight. METHODS: The study included 37 preeclamptic women and 53 normotensive women who considered the control group. Maternal blood samples were withdrawn at 13 weeks of gestation for the measurement of leptin concentrations. Birth weights were transformed to z-scores according to maternal and obstetrical features, based on customized centiles. Non-parametric tests, student's t-test, Pearson's correlation, Spearman's correlation and linear regression analysis were performed in our analysis. RESULTS: Pre-pregnancy body mass index and first trimester maternal plasma leptin levels were significantly higher among women with preeclampsia (p=0.015 and p<0.001, respectively). Birth weight z-score was negatively correlated with leptin levels (r= -0.570, p<0.001), in preeclamptic group and in control group (r= -0.477, p<0.001). The regression modelling demonstrated a significant negative association between birth weight z-scores and leptin for both groups. CONCLUSION: Maternal first trimester serum leptin demonstrates a significant negative association with neonatal weight in preeclamptic pregnancies and to a lesser extent in normotensive pregnancies. A possible leptin's involvement in pathophysiological adaptations that define the foetal growth potential can be supported.

Relation between first trimester maternal serum leptin levels and body mass index in normotensive and pre-eclamptic pregnancies--role of leptin as a marker of pre-eclampsia: a prospective case-control study.

OBJECTIVE: We measured first trimester plasma leptin concentrations in 37 women who subsequently developed pre-eclampsia and 53 normotensive controls to determine the interrelation between leptin and body mass index (BMI) in both groups. We further investigated the association between the risks for pre-eclampsia with maternal leptin levels. METHODS: Bloods samples were collected at 13 weeks. Non-parametric tests, Spearman's correlation, linear regression analysis and multiple logistic regression analysis were applied in our data. RESULTS: 1 kg/m(2) increase in pre-pregnancy BMI was related to a 2.747 (95% CI: 3.242-2.252) ng/ml rise in leptin concentration among cases and 2.502 (95% CI: 2.873-2.131) ng/ml rise in leptin concentrations among controls. Increased leptin concentration (>or=25.3 ng/ml ) in lean women is associated with a 18.8-fold increased risk of pre-eclampsia (adjusted OR: 18.8, CI: 1.8-194, p = 0.014 ). Leptin treated as a continuous variable is a significant predictor of pre-eclampsia (adjusted OR: 1.08, CI: 1.018-1.133, p = 0.009). CONCLUSION: Increased leptin concentration can definitely contribute to the prediction of pre-eclampsia in lean women, but this is not the case in overweight women. Further research in terms of longitudinal case-control studies is required to clarify the predictive value of pre-eclampsia.

Postoperative accelerated radiotherapy with cytoprotection followed by three-dimensional conformal boost in patients with early endometrial/cervical cancer.

AIMS AND BACKGROUND: Adjuvant external beam radiotherapy is highly recommended for uterine carcinomas invading beyond the inner half of the myometrium or cervical stage IIa carcinomas. The addition of a booster intracavitary dose is widely used. METHODS: We assessed the feasibility and toxicity of a hypofractionated accelerated conformal radiotherapy scheme (2.7 Gy per fraction, for 14 consecutive fractions to the pelvis) supported with the cytoprotective agent amifostine (HypoARC). The amifostine dose was individualized (500-1000 mg daily subcutaneously). A booster dose of radiation was given to the vagina and stump using a 6-field 3D-conformal technique (3 x 4 Gy or 4 x 3 Gy) instead of intracavitary radiotherapy. RESULTS: Grade 2 diarrhea appeared in 9/25 (36%) and grade 1 cystitis in 7/25 (28%) cases. Analysis according to the amifostine dose level clearly showed reduced toxicity in patients receiving a daily dose of 750-1000 mg (P < 0.009). Within a median follow-up of 31 months (range, 11-52), there was only one case with grade 2 colitis (the patient had received no amifostine). None of the patients treated has relapsed locally or to distant organs within a median of 31 months of follow-up. CONCLUSIONS: It is concluded that HypoARC followed by 3D-conformal booster dose to the vagina is feasible and convenient for patients and for busy radiotherapy departments, as it reduces the overall time by 50%. When supported by high-dose daily amifostine, it has an impressively low rate of early and late radiation toxicity.

Vascular endothelial growth factor gene polymorphisms and pregnancy.

Vascular endothelial growth factor (VEGF) is a major angiogenic factor and prime regulator of endothelial cell proliferation. During pregnancy, VEGF is essential for the proliferation of trophoblasts, the development of embryonic vasculature and the growth of maternal and fetal blood cells in utero. In cases of pre-eclampsia and in some circumstances of preterm labor-raised umbilical cord serum, VEGF levels might be correlated with the clinical development of the above pathological disorders. Genetic alteration as 936C/T VEGF gene polymorphism has a statistical significant correlation with the severity of pre-eclampsia. The same VEGF gene polymorphism, which has been associated with lower protein production, has an increased risk of spontaneous preterm delivery in a Greek-studied population. Homozygotes were found to carry the greatest risk with a lesser proportionate risk associated with heterozygosity, whereas women with the -1154 allele of the VEGF gene have an increased risk of recurrent pregnancy loss. In this review, we present evidence that demonstrates an implication of VEGF gene polymorphisms in the pathological disorders of pregnancy. However, further genetic studies are needed to confirm these data.

CD30 (Ber-H2) expression by thymocytes and thymic epithelial cells during the late first and second trimester of gestation: an immunohistochemical and in situ hybridization (ISH) study.

BACKGROUND: The exact biological function of CD30 in the thymus during development has been only partially elucidated, although data indicate it may be involved in negative selection. This study was prompted by the observation of a positive reaction of thymic epithelial cells (TECs), Hassall's corpuscles, and thymocytes with the monoclonal antibody CD30 during the late first and second trimester. MATERIAL/METHODS: Twenty paraffin-embedded fetal thymus specimens at the late first and second trimester were investigated by conventional histology and immunohistology for CD30 expression. To provide additional information on the nature and localization of CD30+ thymocytes and CD30+ TECs, in situ hybridization (ISH) was performed on the specimens. RESULTS: 1) In the medulla, a statistically significant difference between CD30+ thymocytes from the late first trimester and those from the second trimester (p<0.0001, t-test) was demonstrated. No significant difference was found concerning CD30+ thymocytes in the cortex. 2) Many medullary TECs and Hassall's corpuscles showed high expression of CD30 during the second trimester, whereas small numbers of CD30+ TECs were found during the late first trimester. No statistically significant difference was found concerning CD30+ TECs in the cortex. CD30 was expressed by ISH in many cells in the medulla and along the septa, whereas the cortex showed little if any expression. Accordingly, a higher CD30 expression was found in medullary than in cortical thymocytes. CONCLUSIONS: Comparison of CD30 expression by TECs and thymocytes during the late first trimester and second trimester suggests an important role for CD30 in thymic selection.

Node-related factors and survival in node-positive breast carcinomas.

The number of positive lymph nodes (+LNs) is the only node-related prognostic factor recognized by the American Joint Committee TNM system for breast cancer. In this study, we evaluated additional node-related prognostic factors in node-positive breast carcinomas. One hundred and thirty-four patients with infiltrating ductal carcinomas and axillary +LNs, who had been treated with modified radical mastectomy, were analyzed. Metastatic lymph nodes were evaluated for traditional prognostic factors, i.e., the number of involved nodes and the extranodal extension, but also for a variety of other node-related characteristics, such as nodal tumor burden and maximum size of tumor deposits, necrosis, stromatogenesis, extranodal vascular involvement, and nodal matting. The results reaffirmed the prognostic significance of metastasis in 1-3 vs. 4-7 axillary lymph nodes and, in addition, revealed the importance of 4 +LNs as a cut-off point for breast tumor aggressiveness, given that survival curves for 4-7 vs. >7 +LNs were indifferent. Interestingly, nodal tumor burden, when extensive, was statistically an adverse prognostic factor. Prognosis was equally poor if metastases to regional nodes showed extensive nodal necrosis or extensive nodal stromatogenesis, if there was extranodal spread, extranodal vascular involvement, or if the axillary +LNs were matted. In multivariate analysis, intranodal necrosis and extranodal vascular involvement were the only node-related features with a significant and independent prognostic function. Node-related pathological features in node-positive breast carcinomas are important in determining prognosis. Intranodal necrosis and extranodal tumor emboli should be considered, in parallel with the number of +LNs, in subsequent treatment design.

Incidence and Detection of Contralateral Breast Cancer.

In this study we estimated the efficacy of contralateral breast biopsy as a subsidiary method of early detection of bilateral breast cancer. We performed blind biopsies in the upper outer quadrant of the opposite breast in 195 patients undergoing surgical treatment for primary breast cancer. The histologic examination of the biopsy specimens showed 12 malignant lesions, which accounts for an incidence of 6.1%. In detail, we had two infiltrating ductal cancers, two infiltrating lobular cancers, three ductal in situ cancers, and five lobular in situ cancers. The overall incidence of invasive disease was 2.05%. We concluded that contralateral breast biopsy should be reconsidered as a method for enhancing early detection of contralateral breast cancer in high-risk groups, especially when it meets the emotional needs of patients. Permission given, it is included in the main surgical treatment of patients, avoiding the cost and complications of anesthesia, and it is cosmetically acceptable, without being an emotional burden for the woman.